Method and system for remedying sensor malfunctions detected by electrochemical impedance spectroscopy

ABSTRACT

A method and system that enables a user to maintain a sensor in real time. The present invention involves performing a diagnostic Electrochemical Impedance Spectroscopy (EIS) procedure to measure sensor impedance value in order to determine if the sensor is operating at an optimal level. If the sensor is not operating at an optimal level, the present invention may further involve performing a sensor remedial action. The sensor remedial action involves reversing the DC voltage being applied between the working electrode and the reference electrode. The reversed DC voltage may be coupled with an AC voltage to extend its reach.

RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 11/618,183, entitled “Method and System for Detecting the Age,Hydration and Functional States of Sensors Using ElectrochemicalImpedance Spectroscopy filed on Dec. 29, 2006, which was acontinuation-in-part of both U.S. patent application Ser. No.11/322,977, entitled “Method of and System for Stabilization of Sensors”filed on Dec. 30, 2005, and U.S. patent application Ser. No. 11/323,242,entitled “Methods and Systems for Detecting the Hydration of Sensors”filed on Dec. 30, 2005, all of which are herein incorporated byreference.

FIELD OF THE INVENTION

Embodiments of this invention relate generally to methods and systems ofusing continuous glucose monitors to measure glucose values. Moreparticularly, embodiments of this invention relate to systems andmethods for remedying sensor malfunctions in real time.

BACKGROUND OF THE INVENTION

Subjects and medical personnel wish to monitor readings of physiologicalconditions within the subject's body. Illustratively, subjects wish tomonitor blood glucose levels in a subject's body on a continuing basis.Presently, a patient can measure his/her blood glucose (BG) using a BGmeasurement device (i.e. glucose meter), such as a test strip meter, acontinuous glucose measurement system (or a continuous glucose monitor),or a hospital hemacue. BG measurement devices use various methods tomeasure the BG level of a patient, such as a sample of the patient'sblood, a sensor in contact with a bodily fluid, an optical sensor, anenzymatic sensor, or a fluorescent sensor. When the BG measurementdevice has generated a BG measurement, the measurement is displayed onthe BG measurement device.

Current continuous glucose measurement systems include subcutaneous (orshort-term) sensors and implantable (or long-term) sensors. For each ofthe short-term sensors and the long-term sensors, a patient has to waita certain amount of time in order for the continuous glucose sensor tostabilize and to provide accurate readings. In many continuous glucosesensors, the subject must wait three hours for the continuous glucosesensor to stabilize before any glucose measurements are utilized. Thisis an inconvenience for the patient and in some cases may cause thepatient not to utilize a continuous glucose measurement system.

Further, when a glucose sensor is first inserted into a patient's skinor subcutaneous layer, the glucose sensor does not operate in a stablestate. The electrical readings from the sensor, which represent theglucose level of the patient, vary over a wide range of readings. In thepast, sensor stabilization used to take several hours. A technique forsensor stabilization is detailed in U.S. Pat. No. 6,809,653, (“the '653patent”), application Ser. No. 09/465,715, filed Dec. 19, 1999, issuedOct. 26, 2004, to Mann et al., assigned to Medtronic Minimed, Inc.,which is incorporated herein by reference. In the '653 patent, theinitialization process for sensor stabilization may be reduced toapproximately one hour. A high voltage (e.g., 1.0-1.2 volts) may beapplied for 1 to 2 minutes to allow the sensor to stabilize and then alow voltage (e.g., between 0.5-0.6 volts) may be applied for theremainder of the initialization process (e.g., 58 minutes or so). Thus,even with this procedure, sensor stabilization still requires a largeamount of time.

It is also desirable to allow electrodes of the sensor to besufficiently “wetted” or hydrated before utilization of the electrodesof the sensor. If the electrodes of the sensor are not sufficientlyhydrated, the result may be inaccurate readings of the patient'sphysiological condition. A user of current blood glucose sensors isinstructed to not power up the sensors immediately. If they are utilizedtoo early, current blood glucose sensors do not operate in an optimal orefficient fashion. No automatic procedure or measuring technique isutilized to determine when to power on the sensor. This manual processis inconvenient and places too much responsibility on the patient, whomay forget to apply or turn on the power source.

Besides the stabilization and wetting problems during the initial sensorlife, there can be additional issues at the during the sensor's life.For instance, the sensor often absorbs polluting species, such aspeptides and small protein molecules during the life of the sensor. Suchpolluting species can reduce the electrode surface area or diffusionpathway of analytes and/or reaction byproducts thus reducing the sensoraccuracy. Determining when such pollutants are effecting the sensorsignal and how to remedy such conditions have not been describedpreviously.

SUMMARY OF THE INVENTION

According to an embodiment of the invention, a method and system ofmaintaining a sensor in real time is described. A diagnostic EISprocedure is performed during the life of a sensor to verify the sensoris functioning normally. The EIS procedure is performed between at leasttwo electrodes of the sensor, which calculates an impedance valuebetween the electrodes, and compares the impedance value against anupper and lower threshold. In preferred embodiments, a diagnostic EISprocedure is performed on a periodic basis throughout the life of thesensor. However, alternatively, a diagnostic EIS procedure can beperformed in addition to or only by an abnormal sensor reading. Inpreferred embodiments, a sensor remedial action is performed if thesensor impedance values fall outside the boundary (defined by an upperand lower threshold). In further embodiments, the sensor remedial actionis the application of a reversed DC voltage. In yet further embodiments,the sensor remedial action is the application of a reversed DC voltagecoupled with an AC voltage. In other words, if the EIS procedure detectsthat the sensor may be polluted, remedial action can be taken, forexample, by applying a reversed DC voltage (DC bias) or a reversed DCvoltage (DC bias) plus an AC signal. In still further embodiments, aftera remedial action is taken, another EIS procedure can be performed todetermine if the sensor has been repaired. If it has not been repaired,the sensor may be terminated or other corrective actions can be taken.

In further embodiments of the present invention, the EIS procedure isused for additional purposes. An initial EIS procedure can be performedduring the sensor initialization stage to determine whether additionalinitialization of the sensor is required or during the sensor hydrationstage to determine whether hydration assist is required. An EISprocedure also may be performed prior to initialization to ensure thatthe sensor is not being reused.

BRIEF DESCRIPTION OF THE DRAWINGS

A detailed description of embodiments of the invention will be made withreference to the accompanying drawings, wherein like numerals designatecorresponding parts in the figures.

FIG. 1 is a perspective view of a subcutaneous sensor insertion set andblock diagram of a sensor electronics device according to an embodimentof the invention;

FIG. 2( a) illustrates a substrate having two sides, a first side whichcontains an electrode configuration and a second side which containselectronic circuitry;

FIG. 2( b) illustrates a general block diagram of an electronic circuitfor sensing an output of a sensor;

FIG. 3 illustrates a block diagram of a sensor electronics device and asensor including a plurality of electrodes according to an embodiment ofthe invention;

FIG. 4 illustrates an alternative embodiment of the invention includinga sensor and a sensor electronics device according to an embodiment ofthe present invention;

FIG. 5 illustrates an electronic block diagram of the sensor electrodesand a voltage being applied to the sensor electrodes according to anembodiment of the present invention;

FIG. 6( a) illustrates a method of applying pulses during stabilizationtimeframe in order to reduce the stabilization timeframe according to anembodiment of the present invention;

FIG. 6( b) illustrates a method of stabilizing sensors according to anembodiment of the present invention;

FIG. 6( c) illustrates utilization of feedback in stabilizing thesensors according to an embodiment of the present invention;

FIG. 7 illustrates an effect of stabilizing a sensor according to anembodiment of the invention;

FIG. 8( a) illustrates a block diagram of a sensor electronics deviceand a sensor including a voltage generation device according to anembodiment of the invention;

FIG. 8( b) illustrates a voltage generation device to implement thisembodiment of the invention;

FIG. 8( c) illustrates a voltage generation device to generate twovoltage values according in a sensor electronics device according toimplement this embodiment of the invention;

FIG. 8( d) illustrates a voltage application device utilized to performmore complex applications of voltage to the sensor.

FIG. 9( a) illustrates a sensor electronics device including amicrocontroller for generating voltage pulses according to an embodimentof the present invention;

FIG. 9( b) illustrates a sensor electronics device including ananalyzation module according to an embodiment of the present invention;

FIG. 10 illustrates a block diagram of a sensor system includinghydration electronics according to an embodiment of the presentinvention;

FIG. 11 illustrates an embodiment of the invention including amechanical switch to assist in determining a hydration time;

FIG. 12 illustrates an electrical detection of detecting hydrationaccording to an embodiment of the invention;

FIG. 13( a) illustrates a method of hydrating a sensor according to anembodiment of the present invention;

FIG. 13( b) illustrates an additional method for verifying hydration ofa sensor according to an embodiment of the present invention;

FIGS. 14( a), (b), (c) illustrate methods of combining hydrating of asensor with stabilizing a sensor according to an embodiment of thepresent invention; and

FIG. 15 illustrates some examples of applied voltage between working andreference electrodes using the EIS technique in accordance withembodiments of the present invention.

FIG. 16 illustrates an example of a Nyquist plot where the selectedfrequencies, from 0.1 Hz to 1000 Mhz AC voltages plus a DC voltage (DCbias) are applied to the working electrode in accordance withembodiments of the present invention.

FIG. 17 illustrates the changing Nyquist plot of sensor impedance as thesensor ages in accordance with embodiments of the present invention.

FIG. 18 illustrates methods of applying EIS technique in stabilizing anddetecting the age of the sensor in accordance with embodiments of thepresent invention.

FIG. 19 illustrates a schedule for performing the EIS procedure inaccordance with embodiments of the present invention.

FIG. 20 illustrates a method of detecting and repairing a sensor usingEIS procedures in conjunction with remedial action in accordance withembodiments of the present invention.

FIGS. 21( a) and (b) illustrate examples of a sensor remedial action inaccordance with the preferred embodiments.

DETAILED DESCRIPTION OF THE INVENTION

In the following description, reference is made to the accompanyingdrawings which form a part hereof and which illustrate severalembodiments of the present inventions. It is understood that otherembodiments may be utilized and structural and operational changes maybe made without departing from the scope of the present inventions.

The present invention described below with reference to flowchartillustrations of methods, apparatus, and computer program products. Itwill be understood that each block of the flowchart illustrations, andcombinations of blocks in the flowchart illustrations, can beimplemented by computer program instructions (as can any menu screensdescribed in the Figures). These computer program instructions may beloaded onto a computer or other programmable data processing apparatus(such as a controller, microcontroller, or processor in a sensorelectronics device to produce a machine, such that the instructionswhich execute on the computer or other programmable data processingapparatus create instructions for implementing the functions specifiedin the flowchart block or blocks. These computer program instructionsmay also be stored in a computer-readable memory that can direct acomputer or other programmable data processing apparatus to function ina particular manner, such that the instructions stored in thecomputer-readable memory produce an article of manufacture includinginstructions which implement the function specified in the flowchartblock or blocks. The computer program instructions may also be loadedonto a computer or other programmable data processing apparatus to causea series of operational steps to be performed on the computer or otherprogrammable apparatus to produce a computer implemented process suchthat the instructions which execute on the computer or otherprogrammable apparatus provide steps for implementing the functionsspecified in the flowchart block or blocks, and/or menus presentedherein.

FIG. 1 is a perspective view of a subcutaneous sensor insertion set anda block diagram of a sensor electronics device according to anembodiment of the invention. As illustrated in FIG. 1, a subcutaneoussensor set 10 is provided for subcutaneous placement of an activeportion of a flexible sensor 12 (see FIG. 2), or the like, at a selectedsite in the body of a user. The subcutaneous or percutaneous portion ofthe sensor set 10 includes a hollow, slotted insertion needle 14, and acannula 16. The needle 14 is used to facilitate quick and easysubcutaneous placement of the cannula 16 at the subcutaneous insertionsite. Inside the cannula 16 is a sensing portion 18 of the sensor 12 toexpose one or more sensor electrodes 20 to the user's bodily fluidsthrough a window 22 formed in the cannula 16. In an embodiment of theinvention, the one or more sensor electrodes 20 may include a counterelectrode, a working electrode, and a reference electrode. Afterinsertion, the insertion needle 14 is withdrawn to leave the cannula 16with the sensing portion 18 and the sensor electrodes 20 in place at theselected insertion site.

In particular embodiments, the subcutaneous sensor set 10 facilitatesaccurate placement of a flexible thin film electrochemical sensor 12 ofthe type used for monitoring specific blood parameters representative ofa user's condition. The sensor 12 monitors glucose levels in the body,and may be used in conjunction with automated or semi-automatedmedication infusion pumps of the external or implantable type asdescribed in U.S. Pat. Nos. 4,562,751; 4,678,408; 4,685,903 or4,573,994, to control delivery of insulin to a diabetic patient.

Particular embodiments of the flexible electrochemical sensor 12 areconstructed in accordance with thin film mask techniques to includeelongated thin film conductors embedded or encased between layers of aselected insulative material such as polyimide film or sheet, andmembranes. The sensor electrodes 20 at a tip end of the sensing portion18 are exposed through one of the insulative layers for direct contactwith patient blood or other body fluids, when the sensing portion 18 (oractive portion) of the sensor 12 is subcutaneously placed at aninsertion site. The sensing portion 18 is joined to a connection portion24 that terminates in conductive contact pads, or the like, which arealso exposed through one of the insulative layers. In alternativeembodiments, other types of implantable sensors, such as chemical based,optical based, or the like, may be used.

As is known in the art, the connection portion 24 and the contact padsare generally adapted for a direct wired electrical connection to asuitable monitor or sensor electronics device 100 for monitoring auser's condition in response to signals derived from the sensorelectrodes 20. Further description of flexible thin film sensors of thisgeneral type are be found in U.S. Pat. No. 5,391,250, entitled METHOD OFFABRICATING THIN FILM SENSORS, which is herein incorporated byreference. The connection portion 24 may be conveniently connectedelectrically to the monitor or sensor electronics device 100 or by aconnector block 28 (or the like) as shown and described in U.S. Pat. No.5,482,473, entitled FLEX CIRCUIT CONNECTOR, which is also hereinincorporated by reference. Thus, in accordance with embodiments of thepresent invention, subcutaneous sensor sets 10 may be configured orformed to work with either a wired or a wireless characteristic monitorsystem.

The sensor electrodes 10 may be used in a variety of sensingapplications and may be configured in a variety of ways. For example,the sensor electrodes 10 may be used in physiological parameter sensingapplications in which some type of biomolecule is used as a catalyticagent. For example, the sensor electrodes 10 may be used in a glucoseand oxygen sensor having a glucose oxidase enzyme catalyzing a reactionwith the sensor electrodes 20. The sensor electrodes 10, along with abiomolecule or some other catalytic agent, may be placed in a human bodyin a vascular or non-vascular environment. For example, the sensorelectrodes 20 and biomolecule may be placed in a vein and be subjectedto a blood stream, or may be placed in a subcutaneous or peritonealregion of the human body.

The monitor 100 may also be referred to as a sensor electronics device100. The monitor 100 may include a power source 110, a sensor interface122, processing electronics 124, and data formatting electronics 128.The monitor 100 may be coupled to the sensor set 10 by a cable 102through a connector that is electrically coupled to the connector block28 of the connection portion 24. In an alternative embodiment, the cablemay be omitted. In this embodiment of the invention, the monitor 100 mayinclude an appropriate connector for direct connection to the connectionportion 104 of the sensor set 10. The sensor set 10 may be modified tohave the connector portion 104 positioned at a different location, e.g.,on top of the sensor set to facilitate placement of the monitor 100 overthe sensor set.

In embodiments of the invention, the sensor interface 122, theprocessing electronics 124, and the data formatting electronics 128 areformed as separate semiconductor chips, however alternative embodimentsmay combine the various semiconductor chips into a single or multiplecustomized semiconductor chips. The sensor interface 122 connects withthe cable 102 that is connected with the sensor set 10.

The power source 110 may be a battery. The battery can include threeseries silver oxide 357 battery cells. In alternative embodiments,different battery chemistries may be utilized, such as lithium basedchemistries, alkaline batteries, nickel metalhydride, or the like, anddifferent number of batteries may used. The monitor 100 provides power,through the power source 110, provides power, through the cable 102 andcable connector 104 to the sensor set. In an embodiment of theinvention, the power is a voltage provided to the sensor set 10. In anembodiment of the invention, the power is a current provided to thesensor set 10. In an embodiment of the invention, the power is a voltageprovided at a specific voltage to the sensor set 10.

FIGS. 2( a) and 2(b) illustrates an implantable sensor and electronicsfor driving the implantable sensor according to an embodiment of thepresent invention. FIG. 2( a) shows a substrate 220 having two sides, afirst side 222 of which contains an electrode configuration and a secondside 224 of which contains electronic circuitry. As may be seen in FIG.2( a), a first side 222 of the substrate comprises two counterelectrode-working electrode pairs 240, 242, 244, 246 on opposite sidesof a reference electrode 248. A second side 224 of the substratecomprises electronic circuitry. As shown, the electronic circuitry maybe enclosed in a hermetically sealed casing 226, providing a protectivehousing for the electronic circuitry. This allows the sensor substrate220 to be inserted into a vascular environment or other environmentwhich may subject the electronic circuitry to fluids. By sealing theelectronic circuitry in a hermetically sealed casing 226, the electroniccircuitry may operate without risk of short circuiting by thesurrounding fluids. Also shown in FIG. 2( a) are pads 228 to which theinput and output lines of the electronic circuitry may be connected. Theelectronic circuitry itself may be fabricated in a variety of ways.According to an embodiment of the present invention, the electroniccircuitry may be fabricated as an integrated circuit using techniquescommon in the industry.

FIG. 2( b) illustrates a general block diagram of an electronic circuitfor sensing an output of a sensor according to an embodiment of thepresent invention. At least one pair of sensor electrodes 310 mayinterface to a data converter 312, the output of which may interface toa counter 314. The counter 314 may be controlled by control logic 316.The output of the counter 314 may connect to a line interface 318. Theline interface 318 may be connected to input and output lines 320 andmay also connect to the control logic 316. The input and output lines320 may also be connected to a power rectifier 322.

The sensor electrodes 310 may be used in a variety of sensingapplications and may be configured in a variety of ways. For example,the sensor electrodes 310 may be used in physiological parameter sensingapplications in which some type of biomolecule is used as a catalyticagent. For example, the sensor electrodes 310 may be used in a glucoseand oxygen sensor having a glucose oxidase enzyme catalyzing a reactionwith the sensor electrodes 310. The sensor electrodes 310, along with abiomolecule or some other catalytic agent, may be placed in a human bodyin a vascular or non-vascular environment. For example, the sensorelectrodes 310 and biomolecule may be placed in a vein and be subjectedto a blood stream.

FIG. 3 illustrates a block diagram of a sensor electronics device and asensor including a plurality of electrodes according to an embodiment ofthe invention. The sensor set or system 350 includes a sensor 355 and asensor electronics device 360. The sensor 355 includes a counterelectrode 365, a reference electrode 370, and a working electrode 375.The sensor electronics device 360 includes a power supply 380, aregulator 385, a signal processor 390, a measurement processor 395, anda display/transmission module 397. The power supply 380 provides power(in the form of either a voltage, a current, or a voltage including acurrent) to the regulator 385. The regulator 385 transmits a regulatedvoltage to the sensor 355. In an embodiment of the invention, theregulator 385 transmits a voltage to the counter electrode 365 of thesensor 355.

The sensor 355 creates a sensor signal indicative of a concentration ofa physiological characteristic being measured. For example, the sensorsignal may be indicative of a blood glucose reading. In an embodiment ofthe invention utilizing subcutaneous sensors, the sensor signal mayrepresent a level of hydrogen peroxide in a subject. In an embodiment ofthe invention where blood or cranial sensors are utilized, the amount ofoxygen is being measured by the sensor and is represented by the sensorsignal. In an embodiment of the invention utilizing implantable orlong-term sensors, the sensor signal may represent a level of oxygen inthe subject. The sensor signal is measured at the working electrode 375.In an embodiment of the invention, the sensor signal may be a currentmeasured at the working electrode. In an embodiment of the invention,the sensor signal may be a voltage measured at the working electrode.

The signal processor 390 receives the sensor signal (e.g., a measuredcurrent or voltage) after the sensor signal is measured at the sensor355 (e.g., the working electrode). The signal processor 390 processesthe sensor signal and generates a processed sensor signal. Themeasurement processor 395 receives the processed sensor signal andcalibrates the processed sensor signal utilizing reference values. In anembodiment of the invention, the reference values are stored in areference memory and provided to the measurement processor 395. Themeasurement processor 395 generates sensor measurements. The sensormeasurements may be stored in a measurement memory (not pictured). Thesensor measurements may be sent to a display/transmission device to beeither displayed on a display in a housing with the sensor electronicsor to be transmitted to an external device.

The sensor electronics device 350 may be a monitor which includes adisplay to display physiological characteristics readings. The sensorelectronics device 350 may also be installed in a desktop computer, apager, a television including communications capabilities, a laptopcomputer, a server, a network computer, a personal digital assistant(PDA), a portable telephone including computer functions, an infusionpump including a display, a glucose sensor including a display, and or acombination infusion pump/glucose sensor. The sensor electronics device350 may be housed in a blackberry, a network device, a home networkdevice, or an appliance connected to a home network.

FIG. 4 illustrates an alternative embodiment of the invention includinga sensor and a sensor electronics device according to an embodiment ofthe present invention. The sensor set or sensor system 400 includes asensor electronics device 360 and a sensor 355. The sensor includes acounter electrode 365, a reference electrode 370, and a workingelectrode 375. The sensor electronics device 360 includes amicrocontroller 410 and a digital-to-analog converter (DAC) 420. Thesensor electronics device 360 may also include a current-to-frequencyconverter (I/F converter) 430.

The microcontroller 410 includes software program code, which whenexecuted, or programmable logic which, causes the microcontroller 410 totransmit a signal to the DAC 420, where the signal is representative ofa voltage level or value that is to be applied to the sensor 355. TheDAC 420 receives the signal and generates the voltage value at the levelinstructed by the microcontroller 410. In embodiments of the invention,the microcontroller 410 may change the representation of the voltagelevel in the signal frequently or infrequently. Illustratively, thesignal from the microcontroller 410 may instruct the DAC 420 to apply afirst voltage value for one second and a second voltage value for twoseconds.

The sensor 355 may receive the voltage level or value. In an embodimentof the invention, the counter electrode 365 may receive the output of anoperational amplifier which has as inputs the reference voltage and thevoltage value from the DAC 420. The application of the voltage levelcauses the sensor 355 to create a sensor signal indicative of aconcentration of a physiological characteristic being measured. In anembodiment of the invention, the microcontroller 410 may measure thesensor signal (e.g., a current value) from the working electrode.Illustratively, a sensor signal measurement circuit 431 may measure thesensor signal. In an embodiment of the invention, the sensor signalmeasurement circuit 431 may include a resistor and the current may bepassed through the resistor to measure the value of the sensor signal.In an embodiment of the invention, the sensor signal may be a currentlevel signal and the sensor signal measurement circuit 431 may be acurrent-to-frequency (I/F) converter 430. The current-to-frequencyconverter 430 may measure the sensor signal in terms of a currentreading, convert it to a frequency-based sensor signal, and transmit thefrequency-based sensor signal to the microcontroller 410. In embodimentsof the invention, the microcontroller 410 may be able to receivefrequency-based sensor signals easier than non-frequency-based sensorsignals. The microcontroller 410 receives the sensor signal, whetherfrequency-based or non frequency-based, and determines a value for thephysiological characteristic of a subject, such as a blood glucoselevel. The microcontroller 410 may include program code, which whenexecuted or run, is able to receive the sensor signal and convert thesensor signal to a physiological characteristic value. In an embodimentof the invention, the microcontroller 410 may convert the sensor signalto a blood glucose level. In an embodiment of the invention, themicrocontroller 410 may utilize measurements stored within an internalmemory in order to determine the blood glucose level of the subject. Inan embodiment of the invention, the microcontroller 410 may utilizemeasurements stored within a memory external to the microcontroller 410to assist in determining the blood glucose level of the subject.

After the physiological characteristic value is determined by themicrocontroller 410, the microcontroller 410 may store measurements ofthe physiological characteristic values for a number of time periods.For example, a blood glucose value may be sent to the microcontroller410 from the sensor every second or five seconds, and themicrocontroller may save sensor measurements for five minutes or tenminutes of BG readings. The microcontroller 410 may transfer themeasurements of the physiological characteristic values to a display onthe sensor electronics device 450. For example, the sensor electronicsdevice 450 may be a monitor which includes a display that provides ablood glucose reading for a subject. In an embodiment of the invention,the microcontroller 410 may transfer the measurements of thephysiological characteristic values to an output interface of themicrocontroller 410. The output interface of the microcontroller 410 maytransfer the measurements of the physiological characteristic values,e.g., blood glucose values, to an external device, e.g., such as aninfusion pump, a combined infusion pump/glucose meter, a computer, apersonal digital assistant, a pager, a network appliance, a server, acellular phone, or any computing device.

FIG. 5 illustrates an electronic block diagram of the sensor electrodesand a voltage being applied to the sensor electrodes according to anembodiment of the present invention. In the embodiment of the inventionillustrated in FIG. 5, an op amp 530 or other servo controlled devicemay connect to sensor electrodes 510 through a circuit/electrodeinterface 538. The op amp 530, utilizing feedback through the sensorelectrodes, attempts to maintain a prescribed voltage (what the DAC maydesire the applied voltage to be) between a reference electrode 532 anda working electrode 534 by adjusting the voltage at a counter electrode536. Current may then flow from a counter electrode 536 to a workingelectrode 534. Such current may be measured to ascertain theelectrochemical reaction between the sensor electrodes 510 and thebiomolecule of a sensor that has been placed in the vicinity of thesensor electrodes 510 and used as a catalyzing agent. The circuitrydisclosed in FIG. 5 may be utilized in a long-term or implantable sensoror may be utilized in a short-term or subcutaneous sensor.

In a long-term sensor embodiment, where a glucose oxidase enzyme is usedas a catalytic agent in a sensor, current may flow from the counterelectrode 536 to a working electrode 534 only if there is oxygen in thevicinity of the enzyme and the sensor electrodes 10. Illustratively, ifthe voltage set at the reference electrode 532 is maintained at about0.5 volts, the amount of current flowing from a counter electrode 536 toa working electrode 534 has a fairly linear relationship with unityslope to the amount of oxygen present in the area surrounding the enzymeand the electrodes. Thus, increased accuracy in determining an amount ofoxygen in the blood may be achieved by maintaining the referenceelectrode 532 at about 0.5 volts and utilizing this region of thecurrent-voltage curve for varying levels of blood oxygen. Differentembodiments of the present invention may utilize different sensorshaving biomolecules other than a glucose oxidase enzyme and may,therefore, have voltages other than 0.5 volts set at the referenceelectrode.

As discussed above, during initial implantation or insertion of thesensor 510, a sensor 510 may provide inaccurate readings due to theadjusting of the subject to the sensor and also electrochemicalbyproducts caused by the catalyst utilized in the sensor. Astabilization period is needed for many sensors in order for the sensor510 to provide accurate readings of the physiological parameter of thesubject. During the stabilization period, the sensor 510 does notprovide accurate blood glucose measurements. Users and manufacturers ofthe sensors may desire to improve the stabilization timeframe for thesensor so that the sensors can be utilized quickly after insertion intothe subject's body or a subcutaneous layer of the subject.

In previous sensor electrode systems, the stabilization period ortimeframe was one hour to three hours. In order to decrease thestabilization period or timeframe and increase the timeliness ofaccuracy of the sensor, a sensor (or electrodes of a sensor) may besubjected to a number of pulses rather than the application of one pulsefollowed by the application of another voltage. FIG. 6( a) illustrates amethod of applying pulses during stabilization timeframe in order toreduce the stabilization timeframe according to an embodiment of thepresent invention. In this embodiment of the invention, a voltageapplication device applies 600 a first voltage to an electrode for afirst time or time period. In an embodiment of the invention, the firstvoltage may be a DC constant voltage. This results in an anodic currentbeing generated. In an alternative embodiment of the invention, adigital-to-analog converter or another voltage source may supply thevoltage to the electrode for a first time period. The anodic currentmeans that electrons are being driven away from electrode to which thevoltage is applied. In an embodiment of the invention, an applicationdevice may apply a current instead of a voltage. In an embodiment of theinvention where a voltage is applied to a sensor, after the applicationof the first voltage to the electrode, the voltage regulator may notapply 605 a voltage for a second time, timeframe, or time period. Inother words, the voltage application device waits until a second timeperiod elapses. The non-application of voltage results in a cathodiccurrent, which results in the gaining of electrons by the electrode towhich the voltage is not applied. The application of the first voltageto the electrode for a first time period followed by the non-applicationof voltage for a second time period is repeated 610 for a number ofiterations. This may be referred to as an anodic and cathodic cycle. Inan embodiment of the invention, the number of total iterations of thestabilization method is three, i.e., three applications of the voltagefor the first time period, each followed by no application of thevoltage three times for the second time period. In an embodiment of theinvention, the first voltage may be 1.07 volts. In an embodiment of theinvention, the first voltage may be 0.535 volts. In an embodiment of theinvention, the first voltage may be approximately 0.7 volts.

The result of the repeated application of the voltage and thenon-application of the voltage results in the sensor (and thus theelectrodes) being subjected to an anodic-cathodic cycle. Theanodic-cathodic cycle results in the reduction of electrochemicalbyproducts which are generated by a patient's body reacting to theinsertion of the sensor or the implanting of the sensor. In anembodiment of the invention, the electrochemical byproducts causegeneration of a background current, which results in inaccuratemeasurements of the physiological parameter of the subject. In anembodiment of the invention, the electrochemical byproduct may beeliminated. Under other operating conditions, the electrochemicalbyproducts may be reduced or significantly reduced. A successfulstabilization method results in the anodic-cathodic cycle reachingequilibrium, electrochemical byproducts being significantly reduced, andbackground current being minimized.

In an embodiment of the invention, the first voltage being applied tothe electrode of the sensor may be a positive voltage. In an embodimentof the invention, the first voltage being applied may be a negativevoltage. In an embodiment of the invention, the first voltage may beapplied to a working electrode. In an embodiment of the invention, thefirst voltage may be applied to the counter electrode or the referenceelectrode.

In embodiments of the invention, the duration of the voltage pulse andthe no application of voltage may be equal, e.g., such as three minuteseach. In embodiments of the invention, the duration of the voltageapplication or voltage pulse may be different values, e.g., the firsttime and the second time may be different. In an embodiment of theinvention, the first time period may be five minutes and the waitingperiod may be two minutes. In an embodiment of the invention, the firsttime period may be two minutes and the waiting period (or secondtimeframe) may be five minutes. In other words, the duration for theapplication of the first voltage may be two minutes and there may be novoltage applied for five minutes. This timeframe is only meant to beillustrative and should not be limiting. For example, a first timeframemay be two, three, five or ten minutes and the second timeframe may befive minutes, ten minutes, twenty minutes, or the like. The timeframes(e.g., the first time and the second time) may depend on uniquecharacteristics of different electrodes, the sensors, and/or thepatient's physiological characteristics.

In embodiments of the invention, more or less than three pulses may beutilized to stabilize the glucose sensor. In other words, the number ofiterations may be greater than 3 or less than three. For example, fourvoltage pulses (e.g., a high voltage followed by no voltage) may beapplied to one of the electrodes or six voltage pulses may be applied toone of the electrodes.

Illustratively, three consecutive pulses of 1.07 volts (followed bythree pulses of no volts) may be sufficient for a sensor implantedsubcutaneously. In an embodiment of the invention, three consecutivevoltage pulses of 0.7 volts may be utilized. The three consecutivepulses may have a higher or lower voltage value, either negative orpositive, for a sensor implanted in blood or cranial fluid, e.g., thelong-term or permanent sensors. In addition, more than three pulses(e.g., five, eight, twelve) may be utilized to create theanodic-cathodic cycling between anodic and cathodic currents in any ofthe subcutaneous, blood, or cranial fluid sensors.

FIG. 6( b) illustrates a method of stabilizing sensors according to anembodiment of the present invention. In the embodiment of the inventionillustrated in FIG. 6( b), a voltage application device may apply 630 afirst voltage to the sensor for a first time to initiate an anodic cycleat an electrode of the sensor. The voltage application device may be aDC power supply, a digital-to-analog converter, or a voltage regulator.After the first time period has elapsed, a second voltage is applied 635to the sensor for a second time to initiate an cathodic cycle at anelectrode of the sensor. Illustratively, rather than no voltage beingapplied, as is illustrated in the method of FIG. 6( a), a differentvoltage (from the first voltage) is applied to the sensor during thesecond timeframe. In an embodiment of the invention, the application ofthe first voltage for the first time and the application of the secondvoltage for the second time are applied 640 for a number of iterations.In an embodiment of the invention, the application of the first voltagefor the first time and the application of the second voltage for thesecond time may each be applied for a stabilization timeframe, e.g., 10minutes, 15 minutes, or 20 minutes rather than for a number ofiterations. This stabilization timeframe is the entire timeframe for thestabilization sequence, e.g., until the sensor (and electrodes) arestabilized. The benefit of this stabilization methodology is a fasterrun-in of the sensors, less background current (in other words asuppression of some the background current), and a better glucoseresponse.

In an embodiment of the invention, the first voltage may be 0.535 voltsapplied for five minutes, the second voltage may be 1.070 volts appliedfor two minutes, the first voltage of 0.535 volts may be applied forfive minutes, the second voltage of 1.070 volts may be applied for twominutes, the first voltage of 0.535 volts may be applied for fiveminutes, and the second voltage of 1.070 volts may be applied for twominutes. In other words, in this embodiment, there are three iterationsof the voltage pulsing scheme. The pulsing methodology may be changed inthat the second timeframe, e.g., the timeframe of the application of thesecond voltage may be lengthened from two minutes to five minutes, tenminutes, fifteen minutes, or twenty minutes. In addition, after thethree iterations are applied in this embodiment of the invention, anominal working voltage of 0.535 volts may be applied.

The 1.08 and 0.535 volts are illustrative values. Other voltage valuesmay be selected based on a variety of factors. These factors may includethe type of enzyme utilized in the sensor, the membranes utilized in thesensor, the operating period of the sensor, the length of the pulse,and/or the magnitude of the pulse. Under certain operating conditions,the first voltage may be in a range of 1.00 to 1.09 volts and the secondvoltage may be in a range of 0.510 to 0.565 volts. In other operatingembodiments, the ranges that bracket the first voltage and the secondvoltage may have a higher range, e.g., 0.3 volts, 0.6 volts, 0.9 volts,depending on the voltage sensitivity of the electrode in the sensor.Under other operating conditions, the voltage may be in a range of 0.8volts to 1.34 volts and the other voltage may be in a range of 0.335 to0.735. Under other operating conditions, the range of the higher voltagemay be smaller than the range of the lower voltage. Illustratively, thehigher voltage may be in a range of 0.9 to 1.09 volts and the lowervoltage may be in a range of 0.235 to 0.835.

In an embodiment of the invention, the first voltage and the secondvoltage may be positive voltages, or alternatively in other embodimentsof the invention, negative voltages. In an embodiment of the invention,the first voltage may be positive and the second voltage may benegative, or alternatively, the first voltage may be negative and thesecond voltage may be positive. The first voltage may be differentvoltage levels for each of the iterations. In an embodiment of theinvention, the first voltage may be a D.C. constant voltage. In otherembodiments of the invention, the first voltage may be a ramp voltage, asinusoid-shaped voltage, a stepped voltage, or other commonly utilizedvoltage waveforms. In an embodiment of the invention, the second voltagemay be a D.C. constant voltage, a ramp voltage, a sinusoid-shapedvoltage, a stepped voltage, or other commonly utilized voltagewaveforms. In an embodiment of the invention, the first voltage or thesecond voltage may be an AC signal riding on a DC waveform. In anembodiment of the invention, the first voltage may be one type ofvoltage, e.g., a ramp voltage, and the second voltage may be a secondtype of voltage, e.g., a sinusoid-shaped voltage. In an embodiment ofthe invention, the first voltage (or the second voltage) may havedifferent waveform shapes for each of the iterations. For example, ifthere are three cycles in a stabilization method, in a first cycle, thefirst voltage may be a ramp voltage, in the second cycle, the firstvoltage may be a constant voltage, and in the third cycle, the firstvoltage may be a sinusoidal voltage.

In an embodiment of the invention, a duration of the first timeframe anda duration of the second timeframe may have the same value, oralternatively, the duration of the first timeframe and the secondtimeframe may have different values. For example, the duration of thefirst timeframe may be two minutes and the duration of the secondtimeframe may be five minutes and the number of iterations may be three.As discussed above, the stabilization method may include a number ofiterations. In embodiments of the invention, during different iterationsof the stabilization method, the duration of each of the firsttimeframes may change and the duration of each of the second timeframesmay change. Illustratively, during the first iteration of theanodic-cathodic cycling, the first timeframe may be 2 minutes and thesecond timeframe may be 5 minutes. During the second iteration, thefirst timeframe may be 1 minute and the second timeframe may be 3minutes. During the third iteration, the first timeframe may be 3minutes and the second timeframe may be 10 minutes.

In an embodiment of the invention, a first voltage of 0.535 volts isapplied to an electrode in a sensor for two minutes to initiate ananodic cycle, then a second voltage of 1.07 volts is applied to theelectrode to the sensor for five minutes to initiate a cathodic cycle.The first voltage of 0.535 volts is then applied again for two minutesto initiate the anodic cycle and a second voltage of 1.07 volts isapplied to the sensor for five minutes. In a third iteration, 0.535volts is applied for two minutes to initiate the anodic cycle and then1.07 volts is applied for five minutes. The voltage applied to thesensor is then 0.535 during the actual working timeframe of the sensor,e.g., when the sensor provides readings of a physiologicalcharacteristic of a subject.

Shorter duration voltage pulses may be utilized in the embodiment ofFIGS. 6( a) and 6(b). The shorter duration voltage pulses may beutilized to apply the first voltage, the second voltage, or both. In anembodiment of the present invention, the magnitude of the shorterduration voltage pulse for the first voltage is −1.07 volts and themagnitude of the shorter duration voltage pulse for the second voltageis approximately half of the high magnitude, e.g., −0.535 volts.Alternatively, the magnitude of the shorter duration pulse for the firstvoltage may be 0.535 volts and the magnitude of the shorter durationpulse for the second voltage is 1.07 volts.

In embodiments of the invention utilizing short duration pulses, thevoltage may not be applied continuously for the entire first timeperiod. Instead, in the first time period, the voltage applicationdevice may transmit a number of short duration pulses during the firsttime period. In other words, a number of mini-width or short durationvoltage pulses may be applied to the electrodes of the sensors over thefirst time period. Each mini-width or short duration pulse may a widthof a number of milliseconds. Illustratively, this pulse width may be 30milliseconds, 50 milliseconds, 70 milliseconds or 200 milliseconds.These values are meant to be illustrative and not limiting. In anembodiment of the invention, such as the embodiment illustrated in FIG.6( a), these short duration pulses are applied to the sensor (electrode)for the first time period and then no voltage is applied for the secondtime period.

In an embodiment of the invention, each short duration pulse may havethe same time duration within the first time period. For example, eachshort duration voltage pulse may have a time width of 50 millisecondsand each pulse delay between the pulses may be 950 milliseconds. In thisexample, if two minutes is the measured time for the first timeframe,then 120 short duration voltage pulses may be applied to the sensor. Inan embodiment of the invention, each of the short duration voltagepulses may have different time durations. In an embodiment of theinvention, each of the short duration voltage pulses may have the sameamplitude values. In an embodiment of the invention, each of the shortduration voltage pulses may have different amplitude values. Byutilizing short duration voltage pulses rather than a continuousapplication of voltage to the sensors, the same anodic and cathodiccycling may occur and the sensor (e.g., electrodes) is subjected to lesstotal energy or charge over time. The use of short duration voltagepulses utilizes less power as compared to the application of continuousvoltage to the electrodes because there is less energy applied to thesensors (and thus the electrodes).

FIG. 6( c) illustrates utilization of feedback in stabilizing thesensors according to an embodiment of the present invention. The sensorsystem may include a feedback mechanism to determine if additionalpulses are needed to stabilize a sensor. In an embodiment of theinvention, a sensor signal generated by an electrode (e.g., a workingelectrode) may be analyzed to determine is the sensor signal isstabilized. A first voltage is applied 630 to an electrode for a firsttimeframe to initiate an anodic cycle. A second voltage is applied 635to an electrode for a second timeframe to initiate a cathodic cycle. Inan embodiment of the invention, an analyzation module may analyze asensor signal (e.g., the current emitted by the sensor signal, aresistance at a specific point in the sensor, an impedance at a specificnode in the sensor) and determine if a threshold measurement has beenreached 637 (e.g., determining if the sensor is providing accuratereadings by comparing against the threshold measurement). If the sensorreadings are determined to be accurate, which represents that theelectrode (and thus the sensor) is stabilized 642, no additionalapplication of the first voltage and/or the second voltage may begenerated. If the stability was not achieved, in an embodiment of theinvention, then an additional anodic/cathodic cycle is initiated by theapplication 630 of a first voltage to an electrode for a first timeperiod and then the application 635 of the second voltage to theelectrode for a second time period.

In embodiments of the invention, the analyzation module may be employedafter an anodic/cathodic cycle of three applications of the firstvoltage and the second voltage to an electrode of the sensor. In anembodiment of the invention, an analyzation module may be employed afterone application of the first voltage and the second voltage, as isillustrated in FIG. 6( c).

In an embodiment of the invention, the analyzation module may beutilized to measure a voltage emitted after a current has beenintroduced across an electrode or across two electrodes. The analyzationmodule may monitor a voltage level at the electrode or at the receivinglevel. In an embodiment of the invention, if the voltage level is abovea certain threshold, this may mean that the sensor is stabilized. In anembodiment of the invention, if the voltage level falls below athreshold level, this may indicate that the sensor is stabilized andready to provide readings. In an embodiment of the invention, a currentmay be introduced to an electrode or across a couple of electrodes. Theanalyzation module may monitor a current level emitted from theelectrode. In this embodiment of the invention, the analyzation modulemay be able to monitor the current if the current is different by anorder of magnitude from the sensor signal current. If the current isabove or below a current threshold, this may signify that the sensor isstabilized.

In an embodiment of the invention, the analyzation module may measure animpedance between two electrodes of the sensor. The analyzation modulemay compare the impedance against a threshold or target impedance valueand if the measured impedance is lower than the target or thresholdimpedance, the sensor (and hence the sensor signal) may be stabilized.In an embodiment of the invention, the analyzation module may measure aresistance between two electrodes of the sensor. In this embodiment ofthe invention, if the analyzation module compares the resistance againsta threshold or target resistance value and the measured resistance valueis less than the threshold or target resistance value, then theanalyzation module may determine that the sensor is stabilized and thatthe sensor signal may be utilized.

FIG. 7 illustrates an effect of stabilizing a sensor according to anembodiment of the invention. Line 705 represents blood glucose sensorreadings for a glucose sensor where a previous single pulsestabilization method was utilized. Line 710 represents blood glucosereadings for a glucose sensor where three voltage pulses are applied(e.g., 3 voltage pulses having a duration of 2 minutes each followed by5 minutes of no voltage being applied). The x-axis 715 represents anamount of time. The dots 720 725 730 and 735 represent measured glucosereadings, taken utilizing a fingerstick and then input into a glucosemeter. As illustrated by the graph, the previous single pulsestabilization method took approximately 1 hour and 30 minutes in orderto stabilize to the desired glucose reading, e.g., 100 units. Incontrast, the three pulse stabilization method took only approximately15 minutes to stabilize the glucose sensor and results in a drasticallyimproved stabilization timeframe.

FIG. 8( a) illustrates a block diagram of a sensor electronics deviceand a sensor including a voltage generation device according to anembodiment of the invention. The voltage generation or applicationdevice 810 includes electronics, logic, or circuits which generatevoltage pulses. The sensor electronics device 360 may also include ainput device 820 to receive reference values and other useful data. Inan embodiment of the invention, the sensor electronics device mayinclude a measurement memory 830 to store sensor measurements. In thisembodiment of the invention, the power supply 380 may supply power tothe sensor electronics device. The power supply 380 may supply power toa regulator 385, which supplies a regulated voltage to the voltagegeneration or application device 810. The connection terminals 811represent that in the illustrated embodiment of the invention, theconnection terminal couples or connects the sensor 355 to the sensorelectronics device 360.

In an embodiment of the invention illustrated in FIG. 8( a), the voltagegeneration or application device 810 supplies a voltage, e.g., the firstvoltage or the second voltage, to an input terminal of an operationalamplifier 840. The voltage generation or application device 810 may alsosupply the voltage to a working electrode 375 of the sensor 355. Anotherinput terminal of the operational amplifier 840 is coupled to thereference electrode 370 of the sensor. The application of the voltagefrom the voltage generation or application device 810 to the operationalamplifier 840 drives a voltage measured at the counter electrode 365 tobe close to or equal the voltage applied at the working electrode 375.In an embodiment of the invention, the voltage generation or applicationdevice 810 could be utilized to apply the desired voltage between thecounter electrode and the working electrode. This may occur by theapplication of the fixed voltage to the counter electrode directly.

In an embodiment of the invention as illustrated in FIGS. 6( a) and6(b), the voltage generation device 810 generates a first voltage thatis to be applied to the sensor during a first timeframe. The voltagegeneration device 810 transmits this first voltage to an op amp 840which drives the voltage at a counter electrode 365 of the sensor 355 tothe first voltage. In an embodiment of the invention, the voltagegeneration device 810 also could transmit the first voltage directly tothe counter electrode 365 of the sensor 355. In the embodiment of theinvention illustrated in FIG. 6( a), the voltage generation device 810then does not transmit the first voltage to the sensor 355 for a secondtimeframe. In other words, the voltage generation device 810 is turnedoff or switched off. The voltage generation device 810 may be programmedto continue cycling between applying the first voltage and not applyinga voltage for either a number of iterations or for a stabilizationtimeframe, e.g., for twenty minutes. FIG. 8( b) illustrates a voltagegeneration device to implement this embodiment of the invention. Thevoltage regulator 385 transfers the regulated voltage to the voltagegeneration device 810. A control circuit 860 controls the closing andopening of a switch 850. If the switch 850 is closed, the voltage isapplied. If the switch 850 is opened, the voltage is not applied. Thetimer 865 provides a signal to the control circuit 860 to instruct thecontrol circuit 860 to turn on and off the switch 850. The controlcircuit 860 includes logic which can instruct the circuit to open andclose the switch 850 a number of times (to match the necessaryiterations). In an embodiment of the invention, the timer 865 may alsotransmit a stabilization signal to identify that the stabilizationsequence is completed, i.e. that a stabilization timeframe has elapsed.

In an embodiment of the invention, the voltage generation devicegenerates a first voltage for a first timeframe and generates a secondvoltage for a second timeframe. FIG. 8( c) illustrates a voltagegeneration device to generate two voltage values according in a sensorelectronics device according to implement this embodiment of theinvention. In this embodiment of the invention, a two position switch870 is utilized. Illustratively, if the first switch position 871 isturned on or closed by the timer 865 instructing the control circuit860, then the voltage generation device 810 generates a first voltagefor the first timeframe. After the first voltage has been applied forthe first timeframe, timer sends a signal to the control circuit 860indicating the first timeframe has elapsed and the control circuit 860directs the switch 870 to move to the second position 872. When theswitch 870 is at the second position 872, the regulated voltage isdirected to a voltage step-down or buck converter 880 to reduce theregulated voltage to a lesser value. The lesser value is then deliveredto the op amp 840 for the second timeframe. After the timer 865 has senta signal to the control circuit 860 that the second timeframe haselapsed, then the control circuit 860 moves the switch 870 back to thefirst position. This continues until the desired number of iterationshas been completed or the stabilization timeframe has elapsed. In anembodiment of the invention, after the sensor stabilization timeframehas elapsed, the sensor transmits a sensor signal 350 to the signalprocessor 390.

FIG. 8( d) illustrates a voltage application device 810 utilized toperform more complex applications of voltage to the sensor. The voltageapplication device 810 may include a control device 860, a switch 890, asinusoid generation device 891, a ramp voltage generation device 892,and a constant voltage generation device 893. In other embodiments ofthe invention, the voltage application may generate an AC wave on top ofa DC signal or other various voltage pulse waveforms. In the embodimentof the invention illustrated in FIG. 8( d), the control device 860 maycause the switch to move to one of the three voltage generation systems891 (sinusoid), 892 (ramp), 893 (constant DC). This results in each ofthe voltage regulation systems generating the identified voltagewaveform. Under certain operating conditions, e.g., where a sinusoidalpulse is to be applied for three pulses, the control device 860 maycause the switch 890 to connect the voltage from the voltage regulator385 to the sinusoid voltage generator 891 in order for the voltageapplication device 810 to generate a sinusoidal voltage. Under otheroperating conditions, e.g., when a ramp voltage is applied to the sensoras the first voltage for a first pulse of three pulses, a sinusoidvoltage is applied to the sensor as the first voltage for a second pulseof the three pulses, and a constant DC voltage is applied to the sensoras the first voltage for a third pulse of the three pulses, the controldevice 860 may cause the switch 890, during the first timeframes in theanodic/cathodic cycles, to move between connecting the voltage from thevoltage generation or application device 810 to the ramp voltagegeneration system 891, then to the sinusoidal voltage generation system892, and then to the constant DC voltage generation system 893. In thisembodiment of the invention, the control device 860 may also bedirecting or controlling the switch to connect certain ones of thevoltage generation subsystems to the voltage from the regulator 385during the second timeframe, e.g., during application of the secondvoltage.

FIG. 9( a) illustrates a sensor electronics device including amicrocontroller for generating voltage pulses according to an embodimentof the present invention. The advanced sensor electronics device mayinclude a microcontroller 410 (see FIG. 4), a digital-to-analogconverter (DAC) 420, an op amp 840, and a sensor signal measurementcircuit 431. In an embodiment of the invention, the sensor signalmeasurement circuit may be a current-to-frequency (I/F) converter 430.In the embodiment of the invention illustrated in FIG. 9( a), softwareor programmable logic in the microcontroller 410 provides instructionsto transmit signals to the DAC 420, which in turn instructs the DAC 420to output a specific voltage to the operational amplifier 840. Themicrocontroller 510 may also be instructed to output a specific voltageto the working electrode 375, as is illustrated by line 911 in FIG. 9(a). As discussed above, the application of the specific voltage tooperational amplifier 840 and the working electrode 375 may drive thevoltage measured at the counter electrode to the specific voltagemagnitude. In other words, the microcontroller 410 outputs a signalwhich is indicative of a voltage or a voltage waveform that is to beapplied to the sensor 355 (e.g., the operational amplifier 840 coupledto the sensor 355). In an alternative embodiment of the invention, afixed voltage may be set by applying a voltage directly from the DAC 420between the reference electrode and the working electrode 375. A similarresult may also be obtained by applying voltages to each of theelectrodes with the difference equal to the fixed voltage appliedbetween the reference and working electrode. In addition, the fixedvoltage may be set by applying a voltage between the reference and thecounter electrode. Under certain operating conditions, themicrocontroller 410 may generates a pulse of a specific magnitude whichthe DAC 420 understands represents that a voltage of a specificmagnitude is to be applied to the sensor. After a first timeframe, themicrocontroller 410 (via the program or programmable logic) outputs asecond signal which either instructs the DAC 420 to output no voltage(for a sensor electronics device 360 operating according to the methoddescribed in FIG. 6( a)) or to output a second voltage (for a sensorelectronics device 360 operating according to the method described inFIG. 6( b)). The microcontroller 410, after the second timeframe haselapsed, then repeats the cycle of sending the signal indicative of afirst voltage to apply, (for the first timeframe) and then sending thesignal to instruct no voltage is to be applied or that a second voltageis to be applied (for the second timeframe).

Under other operating conditions, the microcontroller 410 may generate asignal to the DAC 420 which instructs the DAC to output a ramp voltage.Under other operating conditions, the microcontroller 410 may generate asignal to the DAC 420 which instructs the DAC 420 to output a voltagesimulating a sinusoidal voltage. These signals could be incorporatedinto any of the pulsing methodologies discussed above in the precedingparagraph or earlier in the application. In an embodiment of theinvention, the microcontroller 410 may generate a sequence ofinstructions and/or pulses, which the DAC 420 receives and understandsto mean that a certain sequence of pulses is to be applied. For example,the microcontroller 410 may transmit a sequence of instructions (viasignals and/or pulses) that instruct the DAC 420 to generate a constantvoltage for a first iteration of a first timeframe, a ramp voltage for afirst iteration of a second timeframe, a sinusoidal voltage for a seconditeration of a first timeframe, and a squarewave having two values for asecond iteration of the second timeframe.

The microcontroller 410 may include programmable logic or a program tocontinue this cycling for a stabilization timeframe or for a number ofiterations. Illustratively, the microcontroller 410 may include countinglogic to identify when the first timeframe or the second timeframe haselapsed. Additionally, the microcontroller 410 may include countinglogic to identify that a stabilization timeframe has elapsed. After anyof the preceding timeframes have elapsed, the counting logic mayinstruct the microcontroller to either send a new signal or to stoptransmission of a signal to the DAC 420.

The use of the microcontroller 410 allows a variety of voltagemagnitudes to be applied in a number of sequences for a number of timedurations. In an embodiment of the invention, the microcontroller 410may include control logic or a program to instruct the digital-to-analogconverter 420 to transmit a voltage pulse having a magnitude ofapproximately 1.0 volt for a first time period of 1 minute, to thentransmit a voltage pulse having a magnitude of approximately 0.5 voltsfor a second time period of 4 minutes, and to repeat this cycle for fouriterations. In an embodiment of the invention, the microcontroller 420may be programmed to transmit a signal to cause the DAC 420 to apply thesame magnitude voltage pulse for each first voltage in each of theiterations. In an embodiment of the invention, the microcontroller 410may be programmed to transmit a signal to cause the DAC to apply adifferent magnitude voltage pulse for each first voltage in each of theiterations. In this embodiment of the invention, the microcontroller 410may also be programmed to transmit a signal to cause the DAC 420 toapply a different magnitude voltage pulse for each second voltage ineach of the iterations. Illustratively, the microcontroller 410 may beprogrammed to transmit a signal to cause the DAC 420 to apply a firstvoltage pulse of approximately one volt in the first iteration, to applya second voltage pulse of approximately 0.5 volts in the firstiteration, to apply a first voltage of 0.7 volts and a second voltage of0.4 volts in the second iteration, and to apply a first voltage of 1.2and a second voltage of 0.8 in the third iteration.

The microcontroller 410 may also be programmed to instruct the DAC 420to provide a number of short duration voltage pulses for a firsttimeframe. In this embodiment of the invention, rather than one voltagebeing applied for the entire first timeframe (e.g., two minutes), anumber of shorter duration pulses may be applied to the sensor. In thisembodiment, the microcontroller 410 may also be programmed to programthe DAC 420 to provide a number of short duration voltage pulses for thesecond timeframe to the sensor. Illustratively, the microcontroller 410may send a signal to cause the DAC to apply a number of short durationvoltage pulses where the short duration is 50 milliseconds or 100milliseconds. In between these short duration pulses the DAC may applyno voltage or the DAC may apply a minimal voltage. The DAC 420 may causethe microcontroller to apply the short duration voltage pulses for thefirst timeframe, e.g., two minutes. The microcontroller 410 may thensend a signal to cause the DAC to either not apply any voltage or toapply the short duration voltage pulses at a magnitude of a secondvoltage for a second timeframe to the sensor, e.g., the second voltagemay be 0.75 volts and the second timeframe may be 5 minutes. In anembodiment of the invention, the microcontroller 410 may send a signalto the DAC 420 to cause the DAC 420 to apply a different magnitudevoltage for each of short duration pulses in the first timeframe and/orin the second timeframe. In an embodiment of the invention, themicrocontroller 410 may send a signal to the DAC 420 to cause the DAC420 to apply a pattern of voltage magnitudes to the short durationsvoltage pulses for the first timeframe or the second timeframe. Forexample, the microcontroller may transmit a signal or pulses instructingthe DAC 420 to apply thirty 20 millisecond pulses to the sensor duringthe first timeframe. Each of the thirty 20 millisecond pulses may havethe same magnitude or may have a different magnitude. In this embodimentof the invention, the microcontroller 410 may instruct the DAC 420 toapply short duration pulses during the second timeframe or may instructthe DAC 420 to apply another voltage waveform during the secondtimeframe.

Although the disclosures in FIGS. 6-8 disclose the application of avoltage, a current may also be applied to the sensor to initiate thestabilization process. Illustratively, in the embodiment of theinvention illustrated in FIG. 6( b), a first current may be appliedduring a first timeframe to initiate an anodic or cathodic response anda second current may be applied during a second timeframe to initiatethe opposite anodic or cathodic response. The application of the firstcurrent and the second current may continue for a number of iterationsor may continue for a stabilization timeframe. In an embodiment of theinvention, a first current may be applied during a first timeframe and afirst voltage may be applied during a second timeframe. In other words,one of the anodic or cathodic cycles may be triggered by a current beingapplied to the sensor and the other of the anodic or cathodic cycles maybe triggered by a voltage being applied to the sensor. As describedabove, a current applied may be a constant current, a ramp current, astepped pulse current, or a sinusoidal current. Under certain operatingconditions, the current may be applied as a sequence of short durationpulses during the first timeframe.

FIG. 9( b) illustrates a sensor and sensor electronics utilizing ananalyzation module for feedback in a stabilization period according toan embodiment of the present invention. FIG. 9( b) introduces ananalyzation module 950 to the sensor electronics device 360. Theanalyzation module 950 utilizes feedback from the sensor to determinewhether or not the sensor is stabilized. In an embodiment of theinvention, the microcontroller 410 may include instructions or commandsto control the DAC 420 so that the DAC 420 applies a voltage or currentto a part of the sensor 355. FIG. 9( b) illustrates that a voltage orcurrent could be applied between a reference electrode 370 and a workingelectrode 375. However, the voltage or current can be applied in betweenelectrodes or directly to one of the electrodes and the invention shouldnot be limited by the embodiment illustrated in FIG. 9( b). Theapplication of the voltage or current is illustrated by dotted line 955.The analyzation module 950 may measure a voltage, a current, aresistance, or an impedance in the sensor 355. FIG. 9( b) illustratesthat the measurement occurs at the working electrode 375, but thisshould not be limit the invention because other embodiments of theinvention may measure a voltage, a current, a resistance, or animpedance in between electrodes of the sensor or direct at either thereference electrode 370 or the counter electrode 365. The analyzationmodule 950 may receive the measured voltage, current, resistance, orimpedance and may compare the measurement to a stored value (e.g., athreshold value). Dotted line 956 represents the analyzation module 950reading or taking a measurement of the voltage, current, resistance, orimpedance. Under certain operating conditions, if the measured voltage,current, resistance, or impedance is above the threshold, the sensor isstabilized and the sensor signal is providing accurate readings of aphysiological condition of a patient. Under other operating conditions,if the measured voltage, current, resistance, or impedance is below thethreshold, the sensor is stabilized. Under other operating conditions,the analyzation module 950 may verify that the measured voltage,current, resistance, or impedance is stable for a specific timeframe,e.g., one minute or two minutes. This may represent that the sensor 355is stabilized and that the sensor signal is transmitting accuratemeasurements of a subject's physiological parameter, e.g., blood glucoselevel. After the analyzation module 950 has determined that the sensoris stabilized and the sensor signal is providing accurate measurements,the analyzation module 950 may transmit a signal (e.g., a sensorstabilization signal) to the microcontroller 410 indicating that thesensor is stabilized and that the microcontroller 410 can start using orreceiving the sensor signal from the sensor 355. This is represented bydotted line 957.

FIG. 10 illustrates a block diagram of a sensor system includinghydration electronics according to an embodiment of the presentinvention. The sensor system includes a connector 1010, a sensor 1012,and a monitor or sensor electronics device 1025. The sensor 1010includes electrodes 1020 and a connection portion 1024. In an embodimentof the invention, the sensor 1012 may be connected to the sensorelectronics device 1025 via a connector 1010 and a cable. In otherembodiments of the invention, the sensor 1012 may be directly connectedto the sensor electronics device 1025. In other embodiments of theinvention, the sensor 1012 may be incorporated into the same physicaldevice as the sensor electronics device 1025. The monitor or sensorelectronics device 1025 may include a power supply 1030, a regulator1035, a signal processor 1040, a measurement processor 1045, and aprocessor 1050. The monitor or sensor electronics device 1025 may alsoinclude a hydration detection circuit 1060. The hydration detectioncircuit 1060 interfaces with the sensor 1012 to determine if theelectrodes 1020 of the sensor 1012 are sufficiently hydrated. If theelectrodes 1020 are not sufficiently hydrated, the electrodes 1020 donot provide accurate glucose readings, so it is important to know whenthe electrodes 1020 are sufficiently hydrated. Once the electrodes 1020are sufficiently hydrated, accurate glucose readings may be obtained.

In an embodiment of the invention illustrated in FIG. 10, the hydrationdetection circuit 1060 may include a delay or timer module 1065 and aconnection detection module 1070. In an embodiment of the inventionutilizing the short term sensor or the subcutaneous sensor, after thesensor 1012 has been inserted into the subcutaneous tissue, the sensorelectronics device or monitor 1025 is connected to the sensor 1012. Theconnection detection module 1070 identifies that the sensors electronicsdevice 1025 has been connected to the sensor 1012 and sends a signal tothe timer module 1065. This is illustrated in FIG. 10 by the arrow 1084which represents a detector 1083 detecting a connection and sending asignal to the connection detection module 1070 indicating the sensor1012 has been connected to the sensor electronics device 1025. In anembodiment of the invention where implantable or long-term sensors areutilized, a connection detection module 1070 identifies that theimplantable sensor has been inserted into the body. The timer module1065 receives the connection signal and waits a set or establishedhydration time. Illustratively, the hydration time may be two minutes,five minutes, ten minutes, or 20 minutes. These examples are meant to beillustrative and not to be limiting. The timeframe does not have to be aset number of minutes and can include any number of seconds. In anembodiment of the invention, after the timer module 1065 has waited forthe set hydration time, the timer module 1065 may notify the processor1050 that the sensor 1012 is hydrated by sending a hydration signal,which is illustrated by dotted line 1086.

In this embodiment of the invention, the processor 1050 may receive thehydration signal and only start utilizing the sensor signal (e.g.,sensor measurements) after the hydration signal has been received. Inanother embodiment of the invention, the hydration detection circuit1060 may be coupled between the sensor (the sensor electrodes 1020) andthe signal processor 1040. In this embodiment of the invention, thehydration detection circuit 1060 may prevent the sensor signal frombeing sent to signal processor 1040 until the timer module 1065 hasnotified the hydration detection circuit 1060 that the set hydrationtime has elapsed. This is illustrated by the dotted lines labeled withreference numerals 1080 and 1081. Illustratively, the timer module 1065may transmit a connection signal to a switch (or transistor) to turn onthe switch and let the sensor signal proceed to the signal processor1040. In an alternative embodiment of the invention, the timer module1065 may transmit a connection signal to turn on a switch 1088 (or closethe switch 1088) in the hydration detection circuit 1060 to allow avoltage from the regulator 1035 to be applied to the sensor 1012 afterthe hydration time has elapsed. In other words, in this embodiment ofthe invention, the voltage from the regulator 1035 is not applied to thesensor 1012 until after the hydration time has elapsed.

FIG. 11 illustrates an embodiment of the invention including amechanical switch to assist in determining a hydration time. In anembodiment of the invention, a single housing may include a sensorassembly 1120 and a sensor electronics device 1125. In an embodiment ofthe invention, the sensor assembly 1120 may be in one housing and thesensor electronics device 1125 may be in a separate housing, but thesensor assembly 1120 and the sensor electronics device 1125 may beconnected together. In this embodiment of the invention, a connectiondetection mechanism 1160 may be a mechanical switch. The mechanicalswitch may detect that the sensor 1120 is physically connected to thesensor electronics device 1125. In an embodiment of the invention, atimer circuit 1135 may also be activated when the mechanical switch 1160detects that the sensor 1120 is connected to the sensor electronicsdevice 1125. In other words, the mechanical switch may close and asignal may be transferred to a timer circuit 1135. Once a hydration timehas elapsed, the timer circuit 1135 transmits a signal to the switch1140 to allow the regulator 1035 to apply a voltage to the sensor 1120.In other words, no voltage is applied until the hydration time haselapsed. In an embodiment of the invention, current may replace voltageas what is being applied to the sensor once the hydration time elapses.In an alternative embodiment of the invention, when the mechanicalswitch 1160 identifies that a sensor 1120 has been physically connectedto the sensor electronics device 1125, power may initially be applied tothe sensor 1120. Power being sent to the sensor 1120 results in a sensorsignal being output from the working electrode in the sensor 1120. Thesensor signal may be measured and sent to a processor 1175. Theprocessor 1175 may include a counter input. Under certain operatingconditions, after a set hydration time has elapsed from when the sensorsignal was input into the processor 1175, the processor 1175 may startprocessing the sensor signal as an accurate measurement of the glucosein a subject's body. In other words, the processor 1170 has received thesensor signal from the potentiostat circuit 1170 for a certain amount oftime, but will not process the signal until receiving an instructionfrom the counter input of the processor identifying that a hydrationtime has elapsed. In an embodiment of the invention, the potentiostatcircuit 1170 may include a current-to-frequency converter 1180. In thisembodiment of the invention, the current-to-frequency converter 1180,may receive the sensor signal as a current value and may convert thecurrent value into a frequency value, which is easier for the processor1175 to handle.

In an embodiment of the invention, the mechanical switch 1160 may alsonotify the processor 1170 when the sensor 1120 has been disconnectedfrom the sensor electronics device 1125. This is represented by dottedline 1176 in FIG. 11. This may result in the processor 1170 poweringdown or reducing power to a number of components, chips, and/or circuitsof the sensor electronics device 1125. If the sensor 1120 is notconnected, the battery or power source may be drained if the componentsor circuits of the sensor electronics device 1125 are in a power onstate. Accordingly, if the mechanical switch 1160 detects that thesensor 1120 has been disconnected from the sensor electronics device1125, the mechanical switch may indicate this to the processor 1175, andthe processor 1175 may power down or reduce power to one or more of theelectronic circuits, chips, or components of the sensor electronicsdevice 1125.

FIG. 12 illustrates an electrical method of detection of hydrationaccording to an embodiment of the invention. In an embodiment of theinvention, an electrical detecting mechanism for detecting connection ofa sensor may be utilized. In this embodiment of the invention, thehydration detection electronics 1250 may include an AC source 1255 and adetection circuit 1260. The hydration detection electronics 1250 may belocated in the sensor electronics device 1225. The sensor 1220 mayinclude a counter electrode 1221, a reference electrode 1222, and aworking electrode 1223. As illustrated in FIG. 12, the AC source 1255 iscoupled to a voltage setting device 1275, the reference electrode 1222,and the detection circuit 1260. In this embodiment of the invention, anAC signal from the AC source is applied to the reference electrodeconnection, as illustrated by dotted line 1291 in FIG. 12. In anembodiment of the invention, the AC signal is coupled to the sensor 1220through an impedance and the coupled signal is attenuated significantlyif the sensor 1220 is connected to the sensor electronics device 1225.Thus, a low level AC signal is present at an input to the detectioncircuit 1260. This may also be referred to as a highly attenuated signalor a signal with a high level of attenuation. Under certain operatingconditions, the voltage level of the AC signal may beVapplied*(Ccoupling)/(Ccoupling+Csensor). If the detection circuit 1260detects that the a high level AC signal (lowly attenuated signal) ispresent at an input terminal of the detection circuit 1260, no interruptis sent to the microcontroller 410 because the sensor 1220 has not beensufficiently hydrated or activated. For example, the input of thedetection circuit 1260 may be a comparator. If the sensor 1220 issufficiently hydrated (or wetted), an effective capacitance formsbetween the counter electrode and the reference electrode, (e.g.,capacitance C_(r-c) in FIG. 12) and an effective capacitance formsbetween the reference electrode and the working electrode (e.g.,capacitance C_(w-r) in FIG. 12). In other words, an effectivecapacitance relates to capacitance being formed between two nodes anddoes not represent that an actual capacitor is placed in a circuitbetween the two electrodes. In an embodiment of the invention, the ACsignal from the AC source 1255 is sufficiently attenuated bycapacitances C_(r-c) and C_(w-r) and the detection circuit 1260 detectsthe presence of a low level or highly attenuated AC signal from the ACsource 1255 at the input terminal of the detection circuit 1260. Thisembodiment of the invention is significant because the utilization ofthe existing connections between the sensor 1120 and the sensorelectronics device 1125 reduces the number of connections to the sensor.In other words, the mechanical switch, disclosed in FIG. 11, requires aswitch and associated connections between the sensor 1120 and the sensorelectronics device 1125. It is advantageous to eliminate the mechanicalswitch because the sensor 1120 is continuously shrinking in size and theelimination of components helps achieve this size reduction. Inalternative embodiments of the invention, the AC signal may be appliedto different electrodes (e.g., the counter electrode or the workingelectrode) and the invention may operate in a similar fashion.

As noted above, after the detection circuit 1260 has detected that a lowlevel AC signal is present at the input terminal of the detectioncircuit 1260, the detection circuit 1260 may later detect that a highlevel AC signal, with low attenuation, is present at the input terminal.This represents that the sensor 1220 has been disconnected from thesensor electronics device 1225 or that the sensor is not operatingproperly. If the sensor has been disconnected from the sensorelectronics device 1225, the AC source may be coupled with little or lowattenuation to the input of the detection circuit 1260. As noted above,the detection circuit 1260 may generate an interrupt to themicrocontroller. This interrupt may be received by the microcontrollerand the microcontroller may reduce or eliminate power to one or a numberof components or circuits in the sensor electronics device 1225. Thismay be referred to as the second interrupt. Again, this helps reducepower consumption of the sensor electronics device 1225, specificallywhen the sensor 1220 is not connected to the sensor electronics device1225.

In an alternative embodiment of the election illustrated in FIG. 12, theAC signal may be applied to the reference electrode 1222, as isillustrated by reference numeral 1291, and an impedance measuring device1277 may measure the impedance of an area in the sensor 1220.Illustratively, the area may be an area between the reference electrodeand the working electrode, as illustrated by dotted line 1292 in FIG.12. Under certain operating conditions, the impedance measuring device1277 may transmit a signal to the detection circuit 1260 if a measuredimpedance has decreased to below an impedance threshold or other setcriteria. This represents that the sensor is sufficiently hydrated.Under other operating conditions, the impedance measuring device 1277may transmit a signal to the detection circuit 1260 once the impedanceis above an impedance threshold. The detection circuit 1260 thentransmits the interrupt to the microcontroller 410. In anotherembodiment of the invention, the detection circuit 1260 may transmit aninterrupt or signal directly to the microcontroller.

In an alternative embodiment of the invention, the AC source 1255 may bereplaced by a DC source. If a DC source is utilized, then a resistancemeasuring element may be utilized in place of an impedance measuringelement 1277. In an embodiment of the invention utilizing the resistancemeasuring element, once the resistance drops below a resistancethreshold or a set criteria, the resistance measuring element maytransmit a signal to the detection circuit 1260 (represented by dottedline 1293) or directly to the microcontroller indicating that the sensoris sufficiently hydrated and that power may be applied to the sensor.

In the embodiment of the invention illustrated in FIG. 12, if thedetection circuit 1260 detects a low level or highly attenuated ACsignal from the AC source, an interrupt is generated to themicrocontroller 410. This interrupt indicates that sensor issufficiently hydrated. In this embodiment of the invention, in responseto the interrupt, the microcontroller 410 generates a signal that istransferred to a digital-to-analog converter 420 to instruct or causethe digital-to-analog converter 420 to apply a voltage or current to thesensor 1220. Any of the different sequence of pulses or short durationpulses described above in FIGS. 6( a), 6(b), or 6(c) or the associatedtext describing the application of pulses, may be applied to the sensor1220. Illustratively, the voltage from the DAC 420 may be applied to anop-amp 1275, the output of which is applied to the counter electrode1221 of the sensor 1220. This results in a sensor signal being generatedby the sensor, e.g., the working electrode 1223 of the sensor. Becausethe sensor is sufficiently hydrated, as identified by the interrupt, thesensor signal created at the working electrode 1223 is accuratelymeasuring glucose. The sensor signal is measured by a sensor signalmeasuring device 431 and the sensor signal measuring device 431transmits the sensor signal to the microcontroller 410 where a parameterof a subject's physiological condition is measured. The generation ofthe interrupt represents that a sensor is sufficiently hydrated and thatthe sensor 1220 is now supplying accurate glucose measurements. In thisembodiment of the invention, the hydration period may depend on the typeand/or the manufacturer of the sensor and on the sensor's reaction toinsertion or implantation in the subject. Illustratively, one sensor1220 may have a hydration time of five minutes and one sensor 1220 mayhave a hydration time of one minute, two minutes, three minutes, sixminutes, or 20 minutes. Again, any amount of time may be an acceptableamount of hydration time for the sensor, but smaller amounts of time arepreferable.

If the sensor 1220 has been connected, but is not sufficiently hydratedor wetted, the effective capacitances C_(r-c) and C_(w-r) may notattenuate the AC signal from the AC source 1255. The electrodes in thesensor 1120 are dry before insertion and because the electrodes are dry,a good electrical path (or conductive path) does not exist between thetwo electrodes. Accordingly, a high level AC signal or lowly attenuatedAC signal may still be detected by the detection circuit 1260 and nointerrupt may be generated. Once the sensor has been inserted, theelectrodes become immersed in the conductive body fluid. This results ina leakage path with lower DC resistance. Also, boundary layer capacitorsform at the metal/fluid interface. In other words, a rather largecapacitance forms between the metal/fluid interface and this largecapacitance looks like two capacitors in series between the electrodesof the sensor. This may be referred to as an effective capacitance. Inpractice, a conductivity of an electrolyte above the electrode is beingmeasured. In some embodiments of the invention, the glucose limitingmembrane (GLM) also illustrates impedance blocking electricalefficiency. An unhydrated GLM results in high impedance, whereas a highmoisture GLM results in low impedance. Low impedance is desired foraccurate sensor measurements.

FIG. 13( a) illustrates a method of hydrating a sensor according to anembodiment of the present invention. In an embodiment of the invention,the sensor may be physically connected 1310 to the sensor electronicsdevice. After the connection, in one embodiment of the invention, atimer or counter may be initiated to count 1320 a hydration time. Afterthe hydration time has elapsed, a signal may be transmitted 1330 to asubsystem in the sensor electronics device to initiate the applicationof a voltage to the sensor. As discussed above, in an embodiment of theinvention, a microcontroller may receive the signal and instruct the DACto apply a voltage to the sensor or in another embodiment of theinvention, a switch may receive a signal which allows a regulator toapply a voltage to the sensor. The hydration time may be five minutes,two minutes, ten minutes and may vary depending on the subject and alsoon the type of sensor.

In an alternative embodiment of the invention, after the connection ofthe sensor to the sensor electronics device, an AC signal (e.g., a lowvoltage AC signal) may be applied 1340 to the sensor, e.g., thereference electrode of the sensor. The AC signal may be applied becausethe connection of the sensor to the sensor electronics device allows theAC signal to be applied to the sensor. After application of the ACsignal, an effective capacitance forms 1350 between the electrode in thesensor that the voltage is applied to and the other two electrodes. Adetection circuit determines 1360 what level of the AC signal is presentat the input of the detection circuit. If a low level AC signal (orhighly attenuated AC signal) is present at the input of the detectioncircuit, due to the effective capacitance forming a good electricalconduit between the electrodes and the resulting attenuation of the ACsignal, an interrupt is generated 1370 by the detection circuit and sentto a microcontroller.

The microcontroller receives the interrupt generated by the detectioncircuit and transmits 1380 a signal to a digital-to-analog converterinstructing or causing the digital-to-analog converter to apply avoltage to an electrode of the sensor, e.g., the counter electrode. Theapplication of the voltage to the electrode of the sensor results in thesensor creating or generating a sensor signal 1390. A sensor signalmeasurement device 431 measures the generated sensor signal andtransmits the sensor signal to the microcontroller. The microcontrollerreceives 1395 the sensor signal from the sensor signal measurementdevice, which is coupled to the working electrode, and processes thesensor signal to extract a measurement of a physiological characteristicof the subject or patient.

FIG. 13( b) illustrates an additional method for verifying hydration ofa sensor according to an embodiment of the present invention. In theembodiment of the invention illustrated in FIG. 13( b), the sensor isphysically connected 1310 to the sensor electronics device. In anembodiment of the invention, an AC signal is applied 1341 to anelectrode, e.g., a reference electrode, in the sensor. Alternatively, inan embodiment of the invention, a DC signal is applied 1341 to anelectrode in the sensor. If an AC signal is applied, an impedancemeasuring element measures 1351 an impedance at a point within thesensor. Alternatively, if a DC signal is applied a resistance measuringelement measures 1351 a resistance at a point within the sensor. If theresistance or impedance is lower than an resistance threshold orimpedance threshold, respectively, (or other set criteria), then theimpedance (or resistance) measuring element transmits 1361 (or allows asignal to be transmitted) to the detection circuit, and the detectioncircuit transmits an interrupt identifying that the sensor is hydratedto the microcontroller. The reference numbers 1380, 1390, and 1395 arethe same in FIGS. 13( a) and 13(b) because they represent the sameaction.

The microcontroller receives the interrupt and transmits 1380 a signalto a digital-to-analog converter to apply a voltage to the sensor. In analternative embodiment of the invention, the digital-to-analog convertercan apply a current to the sensor, as discussed above. The sensor, e.g.,the working electrode, creates 1390 a sensor signal, which represents aphysiological parameter of a patient. The microcontroller receives 1395the sensor signal from a sensor signal measuring device, which measuresthe sensor signal at an electrode in the sensor, e.g., the workingelectrode. The microcontroller processes the sensor signal to extract ameasurement of the physiological characteristic of the subject orpatient, e.g., the blood glucose level of the patient.

FIGS. 14( a) and (b) illustrate methods of combining hydrating of asensor with stabilizing of a sensor according to an embodiment of thepresent invention. In an embodiment of the invention illustrated in FIG.14( a), the sensor is connected 1405 to the sensor electronics device.The AC signal is applied 1410 to an electrode of the sensor. Thedetection circuit determines 1420 what level of the AC signal is presentat an input of the detection circuit. If the detection circuitdetermines that a low level of the AC signal is present at the input,(representing a high level of attenuation to the AC signal), aninterrupt is sent 1430 to microcontroller. Once the interrupt is sent tothe microcontroller, the microcontroller knows to begin or initiate 1440a stabilization sequence, i.e., the application of a number of voltagepulses to an electrode of the sensors, as described above. For example,the microcontroller may cause a digital-to-analog converter to applythree voltage pulses (having a magnitude of +0.535 volts) to the sensorwith each of the three voltage pulses followed by a period of threevoltage pulses (having a magnitude of 1.07 volts to be applied). Thismay be referred to transmitting a stabilization sequence of voltages.The microcontroller may cause this by the execution of a softwareprogram in a read-only memory (ROM) or a random access memory. After thestabilization sequence has finished executing, the sensor may generate1450 a sensor signal, which is measured and transmitted to amicrocontroller.

In an embodiment of the invention, the detection circuit may determine1432 that a high level AC signal has continued to be present at theinput of the detection circuit (e.g., an input of a comparator), evenafter a hydration time threshold has elapsed. For example, the hydrationtime threshold may be 10 minutes. After 10 minutes has elapsed, thedetection circuit may still be detecting that a high level AC signal ispresent. At this point in time, the detection circuit may transmit 1434a hydration assist signal to the microcontroller. If the microcontrollerreceives the hydration assist signal, the microcontroller may transmit1436 a signal to cause a DAC to apply a voltage pulse or a series ofvoltage pulses to assist the sensor in hydration. In an embodiment ofthe invention, the microcontroller may transmit a signal to cause theDAC to apply a portion of the stabilization sequence or other voltagepulses to assist in hydrating the sensor. In this embodiment of theinvention, the application of voltage pulses may result in the low levelAC signal (or highly attenuated signal) being detected 1438 at thedetection circuit. At this point, the detection circuit may transmit aninterrupt, as is disclosed in step 1430, and the microcontroller mayinitiate a stabilization sequence.

FIG. 14( b) illustrates a second embodiment of a combination of ahydration method and a stabilization method where feedback is utilizedin the stabilization process. A sensor is connected 1405 to a sensorelectronics device. An AC signal (or a DC signal) is applied 1411 to thesensor. In an embodiment of the invention, the AC signal (or the DCsignal) is applied to an electrode of the sensor, e.g. the referenceelectrode. A impedance measuring device (or resistance measuring device)measures 1416 the impedance (or resistance) within a specified area ofthe sensor. In an embodiment of the invention, the impedance (orresistance) may be measured between the reference electrode and theworking electrode. The measured impedance (or resistance) may becompared 1421 to an impedance or resistance value to see if theimpedance (or resistance) is low enough in the sensor, which indicatesthe sensor is hydrated. If the impedance (or resistance) is below theimpedance (or resistance) value or other set criteria, (which may be athreshold value), an interrupt is transmitted 1431 to themicrocontroller. After receiving the interrupt, the microcontrollertransmits 1440 a signal to the DAC instructing the DAC to apply astabilization sequence of voltages (or currents) to the sensor. Afterthe stabilization sequence has been applied to the sensor, a sensorsignal is created in the sensor (e.g., at the working electrode), ismeasured by a sensor signal measuring device, is transmitted by thesensor signal measuring device, and is received 1450 by themicrocontroller. Because the sensor is hydrated and the stabilizationsequence of voltages has been applied to the sensor, the sensor signalis accurately measuring a physiological parameter (i.e., blood glucose).

FIG. 14( c) illustrates a third embodiment of the invention where astabilization method and hydration method are combined. In thisembodiment of the invention, the sensor is connected 1500 to the sensorelectronics device. After the sensor is physically connected to thesensor electronics device, an AC signal (or DC signal) is applied 1510to an electrode (e.g., reference electrode) of the sensor. At the sametime, or around the same time, the microcontroller transmits a signal tocause the DAC to apply 1520 a stabilization voltage sequence to thesensor. In an alternative embodiment of the invention, a stabilizationcurrent sequence may be applied to the sensor instead of a stabilizationvoltage sequence. The detection circuit determines 1530 what level of anAC signal (or DC signal) is present at an input terminal of thedetection circuit. If there is a low level AC signal (or DC signal),representing a highly attenuated AC signal (or DC signal), present atthe input terminal of the detection circuit, an interrupt is transmitted1540 to the microcontroller. Because the microcontroller has alreadyinitiated the stabilization sequence, the microcontroller receives theinterrupt and sets 1550 a first indicator that the sensor issufficiently hydrated. After the stabilization sequence is complete, themicrocontroller sets 1555 a second indicator indicating the completionof the stabilization sequence. The application of the stabilizationsequence voltages results in the sensor, e.g., the working electrode,creating 1560 a sensor signal, which is measured by a sensor signalmeasuring circuit, and sent to the microcontroller. If the secondindicator that the stabilization sequence is complete is set and thefirst indicator that the hydration is complete is set, themicrocontroller is able to utilize 1570 the sensor signal. If one orboth of the indicators are not set, the microcontroller may not utilizethe sensor signal because the sensor signal may not represent accuratemeasurements of the physiological measurements of the subject.

In further embodiments of the present invention, an ElectrochemicalImpedance Spectroscopy (EIS) technique can be incorporated into the boththe hydration and stabilization routines as another way to determinewhen additional initializations should be applied to help in thehydration and stabilization processes of the sensor. A possible scheduleof EIS procedures is described with respect to FIG. 19. Typically, themicrocontroller will transmit an EIS signal to a digital-to-analogconverter instructing or causing the digital-to-analog converter toapply an AC voltage of various frequencies and a DC bias between theworking and reference electrodes. In preferred embodiments, theelectrochemical impedance spectroscopy (EIS) circuit using the existinghardware is capable of generating an AC voltage between 0.1 Hz to 100KHz, with a programmable amplitude of up to 100 mV, between the workingand reference electrodes. In addition, the EIS circuit is also capableof sampling the current through the working electrode at up to 1 MHzsampling rate. Electrochemical Impedance Spectroscopy is a techniqueused to better characterize the behavior of an electrochemical system,and in particular, an electrode, and thus an improvement of previousmethodology that limited the application to a simple DC current or an ACvoltage of single frequency. FIG. 15 illustrates some examples ofapplied voltage between working and reference electrodes using the EIStechnique. In the examples of FIG. 15, the DC bias is set at 0.535 V,and an AC voltage of varying frequencies are added to the DC bias tocreate a perturbation signal. The amplitude of the AC voltage is fixedat 0.01V. The EIS may be performed at frequencies from μHz to MHz range,but in this invention, only a narrow range of frequencies is needed.Using a current-measuring device, the current passing through theworking electrode can be measured. By dividing the applied voltage bythe current, the impedance of the working electrode can be calculated.

In further preferred embodiment, the use of EIS technique can givevaluable information on the aging of the sensor. Specifically, underdifferent frequencies, the amplitude and the phase angle of theimpedance vary. By plotting the real (X-Axis) and imaginary part(Y-Axis) of the impedance under different frequencies, a Nyquist plotmay be obtained as seen in FIG. 16. Impedance is a measure of oppositionto an alternating or direct current. It is a complex value, i.e., it hasan amplitude and a phase angle, and it has a real and an imaginary part.On a Nyquist Plot, the X value of an impedance is the real impedance,and the Y value of an impedance is the imaginary impedance. The phaseangle is the angle between the impedance point, (X,Y), and the X axis.FIG. 16 illustrates an example of a Nyquist plot where the selectedfrequencies, from 0.1 Hz to 1000 Mhz AC voltages plus a DC voltage (DCbias) are applied between the working electrode and the counterelectrode. Starting from the right, the frequency increases from 0.1 Hz.With each frequency, the real and imaginary impedance can be calculatedand plotted. A typical Nyquist plot of an electrochemical system lookslike a semicircle joined with a straight line, where the semicircle andthe line indicates the plotted impedance. In preferred embodiments, theimpedance at the inflection point is a particular interest since it iseasiest to identify in the Nyquist plot (i.e. where the semicircle meetsthe straight line). Typically the inflection point is close to the Xaxis, and the X value of the inflection point approximates the sum ofpolarization resistance and solution resistance (Rp+Rs). SolutionResistance (Rs) is defined as the resistance of the solution in whichthe electrodes are immersed in, and Polarization Resistance (Rp) isdefined as the voltage between the working electrode and the bulk of thesolution divided by the current flowing through the working electrode.Current flowing through the working electrode is produced as a result ofelectrical voltage being applied to the working electrode such thatelectrochemical reactions occur (i.e., gaining from, or losing to,electrons to the electrode) thus generating the current that flowsthrough the working electrode. Although the preferred embodiment usesthe impedance at the inflection point (i.e. Rp+Rs) to determine theaging, status, stabilization and hydration of the sensor, alternativeembodiments can use any impedance value using either the X value orphase angle as a reference for the particular impedance being used.

In alternative embodiments, a variety of alternative EIS techniques canbe used to measure the impedance of the sensor. For example, a potentialstep, from the normal operating voltage of 0.535 volt to 0.545 volt, canbe applied between the working and reference electrodes. The currentthrough the working electrode can then be measured. In response to thepotential step, the current would spike and then decline. The speed ofcurrent decline provides an alternative way to estimate the impedance,in particular, Rp+Rs.

As seen in FIG. 17, the sensor impedance, in particular, the sum of Rpand Rs, reflects the sensor age as well as the sensor's operatingconditions. Thus, a new sensor normally has higher impedance than a usedsensor as seen from the different plots in FIG. 17. Thus, by looking atthe X-value of the sum of Rp and Rs, a threshold can be used todetermine when the sensor's age has exceeded the specified operatinglife of the sensor. FIG. 17 illustrates an example of Nyquist plot overthe life time of a sensor. The points indicated by arrows are theinflection point. Before initialization, Rs+Rp is higher than 8.5kiloohms, after initialization, the Rs+Rp dropped to below 8 kiloohms.Over the next six days, Rs+Rp continues to decrease, at the end of thespecified sensor life, Rs+Rp dropped below 6.5 kiloohms. Based on suchexamples, a threshold value can be set to specify when Rs+Rp value wouldindicate the end of the specified operating life of the sensor.Therefore, the EIS technique allows the sensor to close the loophole ofallowing the reusing a sensor beyond the specified operating time. Inother words, if the patient attempts to re-use a sensor after the sensorhas reached its specified operating time by disconnecting and thenre-connecting the sensor again, the EIS will measure abnormal lowimpedance. Thereby, the system may then be able to reject the sensor andprompt the patient for a new sensor. Additionally, the use of the EISmay also detect sensor failure by detecting when the sensor's impedancedrops below a low impedance threshold level indicating that the sensormay be too worn to operate normally. The system may then terminate thesensor before the specified operating life. In addition, sensorimpedance can also be used to detect additional sensor failure. Forexample, when a sensor is going into a low-current state (i.e. sensorfailure) due to any variety of reasons, the sensor impedance may alsoincrease beyond a certain high impedance threshold. If the impedancebecomes abnormally high during sensor operation, due to protein orpolypeptide fouling, macrophage attachment or any other factor, thesystem may also terminate the sensor before the specified sensoroperating life.

FIG. 18 illustrates how the EIS technique can be applied during sensorstabilization and detecting the age of the sensor in accordance withembodiments of the present invention. The logic of FIG. 18 begins at1800 after the hydration procedure and sensor initialization proceduredescribed above has been completed. In other words, the sensor has beendeemed to be sufficiently hydrated, and the first initializationprocedure has been applied to initialize the sensor. In preferredembodiments, the initialization procedure is in the form of voltagepulses as described previous in the detailed description. However, inalternative embodiments, different waveforms can be used for theinitialization procedure. For example, a sine wave can be used, insteadof the pulses, to accelerate the wetting or conditioning of the sensor.In addition, it may be necessary for some portion of the waveform to begreater than the normal operating voltage of the sensor, i.e., 0.535volt.

At block 1810, an EIS procedure is applied and the impedance is comparedto both a first high and low threshold. An example of a first high andfirst low threshold value would be 7 kiloohm and 8.5 kiloohm,respectively, although the values can be set higher or lower as needed.If the impedance, for example, Rp+Rs, is higher than the first highthreshold, the sensor undergoes an additional initialization procedure(e.g., the application of one or more additional pulses) at block 1820.Ideally, the number of total initialization procedures given to theinitialize the sensor would be optimized to limit the impact on boththe, battery life of the sensor, and the overall amount of time neededto stabilize a sensor. Thus, by applying the EIS procedure, fewerinitializations can be initially sent, and the number of initializationscan incrementally added to give just the right amount of initializationsto ready the sensor for use. Similarly, in an alternative embodiment,the EIS procedure can be applied to the hydration procedure to minimizethe number of initializations needed to aid the hydration process asdescribed in FIGS. 13-14.

On the other hand, if the impedance, for example Rp+Rs, is below thefirst low threshold, the sensor will be determined to be faulty andwould be terminated immediately at block 1860. A message to the userwill be given to replace the sensor and to begin the hydration processagain. If the impedance is within the high and low threshold, the sensorwill begin to operate normally at block 1830. The logic than proceeds toblock 1840 where an additional EIS is performed to check the age of thesensor. The first time the logic reaches block 1840, the microcontrollerwill perform an EIS to gauge the age of the sensor to close the loopholeof the user being able to plug in and plug out the same sensor. Infuture iterations of the EIS procedure as the logic returns to block1840, the microprocessor will perform an EIS at fixed intervals duringthe specified life of the sensor. In preferred embodiments, the fixedinterval is set for every 2 hours, however, longer or shorter periods oftime can easily be used. At block 1850, the impedance is compared to asecond high and low threshold. An example of a second high and secondlow threshold value would be 5.5 kiloohm and 8.5 kiloohm, respectively,although the values can be set higher or lower as needed. As long as theimpedance values stay within a second high and low threshold, the logicproceeds to block 1830 where the sensor operates normally until thespecified sensor life, for example, 5 days, is reached. Of course, asdescribed with respect to block 1840, EIS will be performed at theregularly scheduled intervals throughout the specified sensor life.However, if after the EIS is performed, the impedance is determined tohave dropped below a second lower threshold or risen above a secondhigher threshold at block 1850, the sensor is terminated at block 1860.In further alternative embodiments, a secondary check can be implementedof a faulty sensor reading. For example, if the EIS indicates that theimpedance is out of the range of the second high and low threshold, thelogic can perform a second EIS to confirm that the second thresholds areindeed not met (and confirm that the first EIS was correctly performed)before determining the end of sensor at block 1860. FIG. 19 builds uponthe above description and details a schedule for EIS procedures.

FIG. 19 illustrates a possible schedule for performing diagnostic EISprocedures in accordance with preferred embodiments of the presentinvention. Each diagnostic EIS procedure is optional and it is possibleto not schedule any diagnostic EIS procedure or to have any combinationof one or more diagnostic EIS procedures, as deemed needed. The scheduleof FIG. 19 begins at sensor insertion at point 1900. Following sensorinsertion at point 1900, the sensor undergoes a hydration period 1910.This hydration period is important because a sensor that is notsufficiently hydrated may give the user inaccurate readings, asdescribed previously. The first optional diagnostic EIS procedure atpoint 1920 is scheduled during this hydration period 1910 to ensure thatthe sensor is sufficiently hydrated. The first diagnostic EIS procedure1920 measures the sensor impedance value to determine if the sensor hasbeen sufficiently hydrated. If the first diagnostic EIS procedure 1920determines impedance is within a set high and low threshold, indicatingsufficient hydration, the sensor controller will allow the sensorpower-up at point 1930. Conversely, if the first diagnostic EISprocedure 1920 determines impedance is outside a set high and lowthreshold, indicating insufficient hydration, the sensor hydrationperiod 1910 may be prolonged. After prolonged hydration, once a certaincapacitance has been reached between the sensor's electrodes, meaningthe sensor is sufficiently hydrated, power-up at point 1930 can occur.

A second optional diagnostic EIS procedure 1940 is scheduled aftersensor power-up at point 1930, but before sensor initialization startsat point 1950. Scheduled here, the second diagnostic EIS procedure 1940can detect if a sensor is being reused prior to the start ofinitialization 1950. The test to see if the sensor is being reused isdetailed in the description of FIG. 18. However, unlike the previousdescription with respect to FIG. 18 where the aging test is performedafter the initialization is completed, the aging test is shown in FIG.19 as being performed before the initialization. It is important toappreciate that the timeline of EIS procedures described in FIG. 19 canbe rearranged without affecting the overall teaching of the application,and the some of the steps can be interchanged in order. As explainedpreviously, the second diagnostic EIS procedure 1940 detects a reusedsensor by determining the sensor's impedance value and then comparing itto a set high and low threshold. If impedance falls outside of the setthreshold, indicating the sensor is being reused, the sensor may then berejected and the user prompted to replace it with a new sensor. The useris thereby prevented from complications arising out of reuse of an oldsensor. If conversely, impedance falls within a set threshold, sensorinitialization 1950 can start with the confidence that a new sensor isbeing used.

A third optional diagnostic EIS procedure 1960 is scheduled afterinitialization starts at point 1950. The third diagnostic EIS procedure1960 tests the sensor's impedance value to determine if the sensor isfully initialized. The third diagnostic EIS procedure 1960 should beperformed at the minimum amount of time needed for any sensor to befully initialized. When performed at this time, sensor life is maximizedby limiting the time a fully initialized sensor goes unused, andover-initialization is averted by confirming full initialization of thesensor before too much initialization occurs. Preventingover-initialization is important because over-initialization results ina suppressed current which can cause inaccurate readings. However,under-initialization is also a problem, so if the third diagnostic EISprocedure 1960 indicates the sensor is under-initialized, an optionalinitialization at point 1970 may be performed in order to fullyinitialize the sensor. Under-initialization is disadvantageous becausean excessive current results that does not relate to the actual glucoseconcentration. Because of the danger of under- and over-initialization,the third diagnostic EIS procedure plays an important role in ensuringthe sensor functions properly when used.

In addition, optional periodic diagnostic EIS procedures 1980 can bescheduled for the time after the sensor is fully initialized. The EISprocedures 1980 can be scheduled at any set interval. They may also bescheduled when triggered by other sensor signals, such as an abnormalcurrent or an abnormal counter electrode voltage. Additionally, as fewor as many EIS procedures 1980 can be scheduled as desired. In preferredembodiments, the EIS procedure used during the hydration process, sensorlife check, initialization process, or the periodic diagnostic tests arethe same procedure. In alternative embodiments, the EIS procedure can beshortened or lengthened (i.e. fewer or more ranges of frequencieschecked) for the various EIS procedures depending on the need to focuson specific impedance ranges. The periodic diagnostic EIS procedures1980 monitor impedance values to ensure that the sensor is continuing tooperate at an optimal level. The sensor may not be operating at anoptimal level if the sensor current has dropped due to pollutingspecies, sensor age, or a combination of polluting species and sensorage. A sensor that has aged beyond a certain length is no longer useful,but a sensor that has been hampered by polluting species can possibly berepaired. Polluting species can reduce the surface area of the electrodeor the diffusion pathways of analytes and reaction byproducts, therebycausing the sensor current to drop. These polluting species are chargedand gradually gather on the electrode or membrane surface under acertain voltage. Previously, polluting species would destroy theusefulness of a sensor. Now, if periodic diagnostic EIS procedures 1980detect impedance values which indicate the presence of pollutingspecies, remedial action can be taken. When remedial action is taken isdescribed with respect to FIG. 20. Periodic diagnostic EIS procedures1980 therefore become extremely useful because they can trigger sensorremedial action which can possibly restore the sensor current to anormal level and prolong the life of the sensor. Two possibleembodiments of sensor remedial actions are described below in thedescriptions of FIGS. 21( a) and 21(b).

Additionally, any scheduled diagnostic EIS procedure 1980 may besuspended or rescheduled when certain events are determined imminent.Such events may include any circumstance requiring the patient to checkthe sensor reading, including for example when a patient measures his orher BG level using a test strip meter in order to calibrate the sensor,when a patient is alerted to a calibration error and the need to measurehis or her BG level using a test strip meter a second time, or when ahyperglycemic or hypoglycemic alert has been issued but notacknowledged.

FIG. 20 illustrates a method of combining diagnostic EIS procedures withsensor remedial action in accordance with preferred embodiments of thepresent invention. The block 2000 diagnostic procedure may be any of theperiodic diagnostic EIS procedure 1980 as detailed in FIG. 19. The logicof this method begins when a diagnostic EIS procedure is performed atblock 2000 in order to detect the sensor's impedance value. In specificembodiments, the EIS procedure applies a combination of a DC bias and anAC voltage of varying frequencies wherein the impedance detected byperforming the EIS procedure is mapped on a Nyquist plot, and aninflection point in the Nyquist plot approximates a sum of polarizationresistance and solution resistance (i.e. the impedance value). After theblock 2000 diagnostic EIS procedure detects the sensor's impedancevalue, the logic moves to block 2010.

At block 2010, the impedance value is compared to a set high and lowthreshold to determine if it is normal. If impedance is within the setboundaries of the high and low thresholds at block 2010, normal sensoroperation is resumed at block 2020 and the logic of FIG. 20 will enduntil a time when another diagnostic EIS procedure is scheduled.Conversely, if impedance is determined to be abnormal (i.e. outside theset boundaries of the high and low thresholds) at block 2010, remedialaction at block 2030 is triggered. An example of a high and lowthreshold value that would be acceptable during a sensor life would be5.5 kiloohm and 8.5 kiloohm, respectively, although the values can beset higher or lower as needed.

The block 2030 remedial action is performed to remove any of thepolluting species, which may have caused the abnormal impedance value.In preferred embodiments, the remedial action is performed by applying areverse current, or a reverse voltage between the working electrode andthe reference electrode. The specifics of the remedial action will bedescribed in more detail with respect to FIG. 21. After the remedialaction is performed at block 2030, impedance value is again tested by adiagnostic EIS procedure at block 2040. The success of the remedialaction is then determined at block 2050 when the impedance value fromthe block 2040 diagnostic EIS procedure is compared to the set high orlow threshold. Like at block 2010, if impedance is within the setthresholds it is deemed normal and if impedance is outside the setthresholds it is deemed abnormal.

If the sensor's impedance value is determined to have been restored tonormal at block 2050, normal sensor operation at block 2020 will occur.If impedance is still not normal, indicating that either sensor age isthe cause of the abnormal impedance or the remedial action wasunsuccessful in removing the polluting species, the sensor is thenterminated at block 2060. In alternative embodiments, instead ofimmediately terminating the sensor, the sensor may generate a sensormessage initially requesting the user to wait and then perform furtherremedial action after a set period of time has elapsed. This alternativestep may be coupled with a separate logic to determine if the impedancevalues are getting closer to being within the boundary of the high andlow threshold after the initial remedial action is performed. Forexample, if no change is found in the sensor impedance values, thesensor may then decide to terminate. However, if the sensor impedancevalues are getting closer to the preset boundary yet still outside theboundary after the initial remedial action, an additional remedialaction could be performed. In yet another alternative embodiment, thesensor may generate a message requesting the user to calibrate thesensor by taking a finger stick meter measurement to further confirmwhether the sensor is truly failing. All of the above embodiments workto prevent a user from using a faulty sensor that produces inaccuratereadings.

Through a combination of diagnostic EIS procedures and remedial action,this method can both detect and possibly repair/correct an inaccuratesensor. It therefore represents a major step forward in the evolutiontowards a more safe and efficient sensor.

FIG. 21( a) illustrates one embodiment of the sensor remedial actionpreviously mentioned. In this embodiment, blockage created by pollutingspecies is removed by reversing the voltage being applied to the sensorbetween the working electrode and the reference electrode. The reversedDC voltage lifts the charged, polluting species from the electrode ormembrane surface, clearing diffusion pathways. With cleared pathways,the sensor's current returns to a normal level and the sensor can giveaccurate readings. Thus, the remedial action saves the user the time andmoney associated with replacing an otherwise effective sensor.

FIG. 21( b) illustrates an alternative embodiment of the sensor remedialaction previously mentioned. In this embodiment, the reversed DC voltageapplied between the working electrode and the reference electrode iscoupled with an AC voltage. By adding the AC voltage, certain tightlyabsorbed species or species on the superficial layer can be removedsince the AC voltage can extend its force further from the electrode andpenetrate all layers of the sensor. The AC voltage can come in anynumber of different waveforms. Some examples of waveforms that could beused include square waves, triangular waves, sine waves, or pulses. Aswith the previous embodiment, once polluting species are cleared, thesensor can return to normal operation, and both sensor life and accuracyare improved.

While the description above refers to particular embodiments of thepresent invention, it will be understood that many modifications may bemade without departing from the spirit thereof. Additional steps andchanges to the order of the algorithms can be made while stillperforming the key teachings of the present invention. For example, thethreshold values may be different depending on what iteration of EISprocedure is being performed (e.g. the initial threshold/boundary checkmay vary from the subsequent threshold/boundary check after a remedialaction is performed). Thus, the accompanying claims are intended tocover such modifications as would fall within the true scope and spiritof the present invention. The presently disclosed embodiments are,therefore, to be considered in all respects as illustrative and notrestrictive, the scope of the invention being indicated by the appendedclaims rather than the foregoing description. All changes that comewithin the meaning of and range of equivalency of the claims areintended to be embraced therein.

What is claimed is:
 1. A method of maintaining a sensor in real time,comprising: inserting a sensor into subcutaneous tissue; hydrating thesensor with interstitial fluid for a hydration period; verifying thesensor is properly hydrated by performing a first diagnosticElectrochemical Impedance Spectroscopy (EIS) procedure during thehydration period; prolonging the hydration period if the firstdiagnostic EIS procedure indicates insufficient hydration, or initiatingsensor power up if the first diagnostic EIS procedure indicatessufficient hydration; and determining whether the sensor is operatingnormally by comparing sensor impedance values to a preset boundaryhaving an upper and a lower threshold value, wherein the firstdiagnostic EIS procedure utilizes a set DC bias and an AC voltage ofvarying frequencies are added to the DC bias to create a perturbationsignal.
 2. The method of claim 1 further comprising: performing anotherdiagnostic EIS procedure on a periodic basis throughout the life of thesensor.
 3. The method of claim 1, wherein an abnormal sensor readingtriggers a subsequent diagnostic EIS procedure.
 4. The method of claim1, further comprising: applying a sensor remedial action if the sensorimpedance values fall outside the boundary.
 5. The method of claim 4,wherein the sensor remedial action applies a reversed DC voltage.
 6. Themethod of claim 4, wherein the sensor remedial action applies a reversedDC voltage coupled with an AC voltage.
 7. The method of claim 4, furthercomprising: performing an additional diagnostic EIS procedure todetermine updated sensor impedance values after applying the remedialaction; and comparing the updated sensor impedance values to theboundary to determine if the sensor impedance values fall within theboundary.
 8. The method of claim 7, further comprising: terminating theuse of the sensor if the updated sensor impedance values fall outsidethe boundary.
 9. The method of claim 7, further comprising: generating amessage requesting the user to calibrate the sensor if the updatedsensor impedance values fall outside the boundary.
 10. The method ofclaim 7, further comprising: waiting and performing remedial actionagain if impedance values indicate the earlier remedial action waspartially successful but impedance values still do not fall within theboundary.
 11. A system to maintain an implantable sensor in real time,comprising: a means for performing a diagnostic EIS procedure during thelife of a sensor to derive sensor impedance values; and a sensorimplanted into subcutaneous tissue, the sensor having an electrodeconfiguration to generate sensor signals as a result of performing aplurality of diagnostic EIS procedures during the life of the sensor;electronic circuitry to determine whether the sensor is operatingnormally by comparing the sensor impedance values to a preset boundaryhaving an upper and a lower threshold value, wherein the plurality ofEIS procedures utilize a set DC bias and an AC voltage of varyingfrequencies are added to the DC bias to create a perturbation signal.12. The system of claim 11, wherein the plurality of diagnostic EISprocedures is performed on a periodic basis throughout the life of thesensor.
 13. The system of claim 11, wherein one of the plurality ofdiagnostic EIS procedures is triggered by an abnormal sensor reading.14. The system of claim 11, wherein a sensor remedial action isinitiated if the sensor impedance values fall outside the boundary. 15.The system of claim 14, wherein the sensor remedial action applies areversed DC voltage.
 16. The system of claim 14, wherein the sensorremedial action applies a reversed DC voltage coupled with an ACvoltage.
 17. The system of claim 14, wherein an additional diagnosticEIS procedure is performed to determine updated sensor impedance valuesafter applying the remedial action; and the updated sensor impedancevalues are compared to the boundary to determine if the sensor impedancevalues fall within the boundary.
 18. The system of claim 17, wherein theuse of the sensor is terminated if the updated sensor impedance valuesfall outside the boundary.
 19. The system of claim 17, wherein a messagerequesting the user to calibrate the sensor is generated if the updatedsensor impedance values fall outside the boundary.
 20. The system ofclaim 17, wherein another remedial action is performed if the updatedsensor impedance values indicate a previous remedial action waspartially successful but the updated sensor impedance values still donot fall within the boundary.